Composite Histiocytic Sarcoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma of the Ocular Adnexa.

Histiocytic sarcoma (HS) is a rare and aggressive hematologic neoplasm characterized by the proliferation of malignant histiocytes. It infrequently presents with periorbital involvement. Here we present the first documented case of ocular adnexal histiocytic sarcoma composite with chronic lymphocytic leukemia/small lymphocytic lymphoma and provide compelling evidence for the transdifferentiation of chronic lymphocytic leukemia/small lymphocytic lymphoma to histiocytic sarcoma in an 80-year-old woman. Comprehending the clinicopathological characteristics of histiocytic sarcoma and various other histiocytic proliferations and neoplasms affecting orbital and ocular structures is imperative for ophthalmic surgeons and pathologists.

Using three-dimensional printed models for trainee orbital fracture education.

BACKGROUND: Three-dimensional printing is an underutilized technology in ophthalmology training; its use must be explored in complex educational scenarios. This study described a novel approach to trainee education of orbital fracture repair utilizing three-dimensional (3D) printed models as a teaching tool. METHODS: Ophthalmology residents and oculoplastic fellows from multiple training institutions underwent an educational session on orbital fractures, learning through four different models. Participants analyzed orbital fractures through computerized tomography (CT) imaging alone and then utilizing CT imaging with the aid of a 3D printed model. Participants completed a questionnaire assessing their understanding of the fracture pattern and surgical approach. After the training, participants were surveyed on the impact of the educational session. Components of the training were rated by participants on a 5-point Likert scale. RESULTS: A statistically significant difference (p < .05) was found in participant confidence conceptualizing the anatomic boundaries of the fracture and planning the orbital fracture approach for repair of three out of four models on pre-test post-test analysis. On exit questionnaire, 84.3% of participants thought the models were a useful tool for surgical planning, 94.8% of participants thought the models were a useful tool for conceptualizing the anatomic boundaries of the fracture, 94.8% of participants thought the models were a useful tool for orbital fracture training, and 89.5% of participants thought the exercise was helpful. CONCLUSION: This study supports the value of 3D printed models of orbital fractures as an effective tool for ophthalmology trainee education to improve understanding and visualization of complex anatomical space and pathology. Given the limited opportunities trainees may have for hands-on orbital fracture practice, 3D printed models provide an accessible way to enhance training.

Thyroid Eye Disease and its Vision-Threatening Manifestations in the Academy IRIS Registry: 2014-2018.

PURPOSE: To evaluate prevalence of thyroid eye disease (TED) and associated factors in the American Academy of Ophthalmology IRISⓇ Registry (Intelligent Research in Sight). DESIGN: Cross-sectional analysis of the IRIS Registry. METHODS: IRIS Registry patients (18-90 years old) were classified as TED (ICD-9: 242.00, ICD-10: E05.00 on ≥2 visits) or non-TED cases, and prevalence was estimated. Odds ratios (OR) and 95% Confidence Intervals (CIs) were estimated using logistic regression. RESULTS: 41,211 TED patients were identified. TED prevalence was 0.09%, showed a unimodal age distribution (highest prevalence in ages 50-59 years (y) (0.12%)), higher rates in females than males (0.12% vs. 0.04%) and in non-Hispanics than Hispanics (0.10% vs. 0.05%). Prevalence differed by race (from 0.08% in Asians to 0.12% in Black/African-Americans), with varying peak ages of prevalence. Factors associated with TED in multivariate analysis included age: ((18-<30y (reference), 30-39y: OR (95%CI) 2.2 (2.0, 2.4), 40-49y: 2.9 (2.7,3.1), 50-59y: 3.3 (3.1, 3. 5), 60-69y: 2.7 (2.54, 2.85), 70+: 1.5 (1.46, 1.64)); female sex vs male (reference), 3.5 (3.4,3.6), race: White (reference), Blacks: 1.1 (1.1,1.2), Asian: 0.9 (0.8,0.9), Hispanic ethnicity vs not Hispanic (reference), 0.68 (0.6,0.7), smoking status: (never (ref), former: 1.64 (1.6,1.7), current 2.16: (2.1,2.2)) and Type 1 diabetes (yes vs no (reference): 1.87 (1.8, 1.9). CONCLUSIONS: This epidemiologic profile of TED includes new observations such as a unimodal age distribution and racial variation in prevalence. Associations with female sex, smoking, and Type 1 diabetes are consistent with prior reports. These findings raise novel questions about TED in different populations.

Geographic and socioeconomic access disparities to Phase 3 clinical trials in ophthalmology in the United States.

BACKGROUND/OBJECTIVE: To identify geographic and socioeconomic variables associated with residential proximity to Phase 3 ophthalmology clinical trial sites. METHODS: The geographic location of clinical trial sites for Phase 3 clinical trials in ophthalmology was identified using ClinicalTrials.gov. Driving time from each United States (US) census tract centroid to nearest clinical trial site was calculated using real traffic patterns. Travel data were crosslinked to census-tract level public datasets from United States Census Bureau American Community Survey (ACS). Cross-sectional multivariable regression was used to identify associations between census-tract sociodemographic factors and driving time (>60 min) from each census tract centroid to the nearest clinical trial site. RESULTS: There were 2330 unique clinical trial sites and 71,897 census tracts. Shortest median time was to retina sites [33.7 min (18.7, 70.1 min)]. Longest median time was to neuro-ophthalmology sites [119.8 min (48.7, 240.4 min)]. Driving >60 min was associated with rural tracts [adjusted odds ratio (aOR) 7.60; 95% CI (5.66-10.20), p < 0.0001]; Midwest [aOR 1.84(1.15-2.96), p = 0.01], South [aOR 2.57 (1.38-4.79), p < 0.01], and West [aOR 2.52 (1.52-4.17), p < 0.001] v. Northeast; and tracts with higher visual impairment [aOR 1.07 (1.03-1.10), p < 0.001)]; higher poverty levels [4th v.1st Quartile of population below poverty, aOR 2.26 (1.72-2.98), p < 0.0001]; and lower education levels [high school v. Bachelor's degree or higher aOR 1.02 (1.00-1.03), p = 0.0072]. CONCLUSIONS: There are significant geographic and socioeconomic disparities in access to ophthalmology clinical trial sites for rural, non-Northeastern, poorer, and lower education level census tracts, and for census tracts with higher levels of self-reported visual impairment.

Cyclin D1 Expression and Molecular Genetic Findings in Periocular Histiocytoses and Neoplasms of Macrophage-Dendritic Cell Lineage.

PURPOSE: Frequent activating mutations in the mitogen-activated protein kinase (MAPK) pathway genes have been identified in histiocytoses. MAPK signaling consistently upregulates cyclin D1. The goal of this study was to determine whether cyclin D1 expression by immunohistochemistry is a useful diagnostic marker for periocular histiocytoses and to further characterize their genetic basis. DESIGN: Retrospective observational case series. METHODS: Pathology records were searched for all patients with histiocytoses diagnosed between 1995 and 2020. Eleven histiocyte-rich inflammatory lesions and 10 xanthelasma served as controls. Cyclin D1 immunohistochemistry was performed on all tissues. A subset of histiocytoses was evaluated by next-generation sequencing (NGS) and droplet digital PCR (ddPCR). RESULTS: There were 36 patients, 15 males (42%) and 21 females (58%), with histiocytoses: 9 juvenile xanthogranuloma (25%), 8 adult-onset asthma and periocular xanthogranuloma (22%), 7 Langerhans cell histiocytosis (19%), 5 Rosai-Dorfman disease (14%), 5 xanthogranuloma-not otherwise specified (14%), 1 Erdheim-Chester disease (3%), and 1 histiocytic sarcoma (3%). Moderate to strong nuclear cyclin D1 expression was present in ≥50% of lesional cells in histiocytoses (23/36, 64%), significantly more when compared to histiocyte-rich inflammatory lesions (0/11, 0%, P<.001) and xanthelasma (0/10, 0%, P<.001). Cyclin D1 was expressed in <10% of lesional cells in all 11 histiocyte-rich inflammatory lesions (P<.001) and all 10 xanthelasma lesions (P<.001). MAPK pathway gene mutations were detected in 12 of 14 (86%) histiocytoses successfully assayed by NGS and/or ddPCR. CONCLUSIONS: Our study confirms that the cyclin D1 immunohistochemical stain is a useful diagnostic marker for periocular histiocytoses, correlating with underlying mutations in MAPK pathway genes.

Complications Associated with Polydek Sutures Used in Eyelid Lateral Tarsal Strip Procedures.

Suture-related complications can occur in response to a patient's immune system activation regardless of surgical site. However, there is minimal literature describing complications related to commonly used Polydek sutures. We report the diagnosis, treatment, and follow up of four cases of Polydek suture-related complications post-eyelid lateral tarsal strip procedures, including an early wound healing problem/infection and later granuloma formation and/or suture extrusion that only resolved after removal of the Polydek suture or granuloma tissue. Use of non-Polydek sutures may reduce the likelihood for post-operative suture complications.

Mucoepidermoid Carcinoma of the Lacrimal Sac: Clinical-Pathologic Analysis, Including Molecular Genetics.

PURPOSE: The aim of this study was to assess whether mucoepidermoid carcinoma of the lacrimal sac is a counterpart of CRTC1/3-MAML2 gene fusion-related salivary gland mucoepidermoid carcinoma. METHODS: In this retrospective observational case series, pathology records were searched for all cases of lacrimal sac mucoepidermoid carcinoma diagnosed between 1990 and 2018. Data collected included demographics, clinical findings, management, and follow-up. Pathologic parameters assessed included tumor morphology, immunohistochemistry, and MAML2 and EGFR fluorescence in situ hybridization (FISH) studies. RESULTS: Six patients with mucoepidermoid carcinoma of the lacrimal sac, 5 males and 1 female, with a median age of 63 years (range 24-66) were identified. Five tumors were managed with radical resection and 1 patient underwent orbital exenteration. None of the patients developed recurrence or metastases with an average follow-up of 18 months (range 13-23). All tumors had morphologic and immunohistochemical features of mucoepidermoid carcinoma and overexpressed EGFR. MAML2 FISH was negative for MAML2 rearrangement in all tumors. EGFR FISH demonstrated EGFR amplification in 1 tumor. CONCLUSIONS: Mucoepidermoid carcinoma of the lacrimal sac is not a lacrimal sac counterpart of CRTC1/3-MAML2 gene fusion-related salivary gland mucoepidermoid carcinoma. EGFR pathway activation and EGFR amplification in a subset of these neoplasms suggest the potential role for anti-EGFR agents.

Treatment of mucous membrane pemphigoid with mycophenolate mofetil.

PURPOSE: To evaluate the clinical outcomes of mycophenolate mofetil (MMF) treatment of mucous membrane pemphigoid (MMP). METHODS: This is a retrospective analysis of consecutive patients with clinical MMP seen in the Ocular Surface Disease Clinic at the Wills Eye Institute, between January 1, 2004, and December 31, 2010, treated with MMF. The main outcomes measured were control of inflammation and discontinuation of MMF. RESULTS: A total of 23 MMP patients taking MMF were identified. The median age of the MMF-treated patients was 77.0 years. Eleven of the 23 patients (47.8%) had biopsy-proven MMP. All patients were at least Foster grading system stage 2, with most stage 3 or 4. Eight patients (34.8%) failed previous treatments with dapsone, methotrexate, prednisone, azathioprine, cyclophosphamide, or 6-mercaptopurine. The average duration of MMF treatment was 23.32 ± 33.17 months (range 1-124.83 months, median 7.4 months). Of the 23 patients with MMP, control of inflammation was achieved with MMF within 3 months for 56.5% [95% confidence interval (CI) 54.5-59.6], within 6 months for 69.6% (95% CI 65.2-76.6), and within 12 months for 82.6% (95% CI 75.3-92.4) of the patients. Nineteen patients (82.4%) achieved control of inflammation, with 16 of the 19 (84.2%) achieving control of inflammation with MMF as monotherapy. Fifteen patients were treated with MMF as initial therapy. Twenty-one percent of patients (5 of 23) were taken off MMF for failure of inflammatory control (4) or an allergic reaction (1). CONCLUSIONS: Treatment of MMP with MMF in this uncontrolled case series resulted in control of inflammation in the majority of patients with minimal side effects. Our data support consideration of MMF as an initial treatment option for active ocular MMP.

Giant fornix syndrome: a case series.

PURPOSE: To describe the demographics, characteristics, and treatment of giant fornix syndrome, a rare cause of chronic purulent conjunctivitis in the elderly. METHODS: Retrospective chart review of five patients with giant fornix syndrome evaluated by the Cornea Service, Oculoplastics and Orbital Surgery Service and the Department of Pathology at the Wills Eye Institute. RESULTS: The median age of the 5 female patients was 75 years (mean 80, range 70-95). The median duration of eye symptoms before presentation was 2 years (mean 2.4, range 1-4). Before referral, the chronic conjunctivitis was treated with topical antibiotics in all 5 cases and with additional dacryocystorhinostomy in one case. The right eye was affected in 2 cases, and the left eye was affected in the other 3 cases. Floppy eyelids were present in 2 cases. The superior fornix was involved in 4 cases, and the inferior fornix was involved in one case. Pseudomembranes and superficial punctate keratitis (SPK) were seen in 3 cases. Diagnosis of giant fornix syndrome was made in all 5 cases. Conjunctival culture grew methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and S. aureus in singular cases. Case 1 was treated with topical moxifloxacin, Case 2 was treated with topical vancomycin and repair of the upper eyelid, Case 3 was treated with topical besifloxacin, and Case 4 was treated with dacryocystorhinostomy and topical vancomycin. Case 5 was treated with reconstruction of the left upper eyelid. The median duration of follow up was 4 months (mean 21.6, range 1-84). CONCLUSIONS: Giant fornix syndrome can lead to chronic relapsing conjunctivitis in the elderly. Deep conjunctival fornices in affected patients can be a site for prolonged sequestration of bacteria causing recurrent infections. Removing the infected debris from the superior fornix and reconstruction of the upper eyelid may prevent the recurrent chronic persistent infection.

Extrusion of hydrogel exoplant into upper eyelid 16 years after a scleral buckle procedure.

Sixteen years after scleral buckle surgery with a hydrogel episcleral exoplant, a 43-year-old woman presented with progressive binocular diplopia, ptosis, and an expanding mass in her upper eyelid. She underwent surgical removal of the hydrogel exoplant through an anterior approach. The exoplant proved to be friable, fragmented, and encapsulated in a fibrous tissue; the exoplant was removed in its entirety. Postoperatively, the eyelid mass resolved, while her diplopia and ptosis improved slightly.

Wooden intraorbital foreign body injuries: clinical characteristics and outcomes of 23 patients.

PURPOSE: To describe the clinical characteristics, interventions, and visual outcomes of orbital injuries associated with wooden foreign bodies. METHODS: A retrospective case review of orbital injuries managed at Wills Eye Institute and Massachusetts Eye and Ear Infirmary was conducted between 1992 and 2006. RESULTS: The clinical course and management for a total of 23 intraorbital wooden foreign body injuries were reviewed. The distribution of wood included pencil (39%), tree branch/plant matter (35%), and other treated wood (26%). About half of the subjects (52%) presented with preoperative vision between 20/20 and 20/40. Almost all [corrected] of the subjects with preoperative vision between 20/20 to 20/40 retained vision in that range postoperatively (92%). [corrected] Time from injury to presentation was highly variable, ranging from 24 hours to 17 months (mean, 62 days; median, 3 days). Forty-three percent of subjects presented within 24 hours of injury. The site of foreign body found within the orbit was superior (26%; n = 6), medial 30% (n = 7), inferior (26%, n = 6), posterior (9%; n = 2), and lateral (4%; n = 1). Preliminary radiographic interpretation for foreign body was definite in 61% (n = 14), possible in 22% (n = 5), and absent in 13% (n = 3). CONCLUSIONS: Young men are at particularly high risk for wood intraorbital foreign body. There was a relatively equal distribution of wood type. The time from injury to presentation was variable, ranging from <1 day to over a year. Almost half of the subjects presented within 24 hours of injury. In patients with a known site of penetration, almost half occurred in the conjunctiva, notably without presence of eyelid laceration, emphasizing the need to check the conjunctiva and fornices closely. Preliminary radiographic readings often miss or are inconclusive in detecting the foreign body. The shape, location, serial examinations, and particularly the use of quantitative CT are extremely helpful in distinguishing retained wood foreign body from other low-density signals of air or fat.

Evaluation and management of pediatric orbital fractures in a primary care setting.

OBJECTIVE: To review and evaluate the management of white-eyed blowout fractures (WEBOF) from Emergency Department (ED) triage through surgical repair. METHODS: Retrospective chart review of consecutive cases of pediatric orbital blowout fracture requiring surgical repair at a large ophthalmologic referral center. The characteristics of patients with WEBOF and those with conventional orbital blowout fractures were compared, including: mechanism of injury, clinical presentation, ED management and referral patterns, and time to definitive treatment. RESULTS: Sixteen patients comprised the WEBOF study group, and 14 patients with conventional blowout fractures comprised the control group. All WEBOF had pain with eye movement, limited ductions and diplopia, and 75% had nausea and vomiting. These symptoms were present in significantly lower frequencies in control patients (64%, 64%, 7%, 14%, respectively). Compared to controls, WEBOF patients were younger; had injury more often resulting from sports and play; were less likely to undergo orbital imaging in the ED; were more likely to be diagnosed with concussion in the ED; were less likely to be seen urgently by an ophthalmologist; and were told to follow-up with an ophthalmologist 4-5 days later than control patients. CONCLUSIONS: WEBOF is a clinical diagnosis consisting of vertical diplopia, gaze restriction and nausea and/or vomiting in the setting of peri-orbital trauma in the pediatric and young-adult age group. The paucity of external signs of trauma may lead to initial misdiagnosis and delay in treatment. All patients who meet WEBOF criteria should undergo dedicated orbital CT as part of the ED evaluation. If WEBOF is suspected, a prompt referral to an ophthalmologist should be made.

Alveolar rhabdomyosarcoma presenting as an acute orbital mass in the medial rectus muscle.

Rhabdomyosarcoma is the most common pediatric primary neoplasm in the orbit, often presenting with rapid proptosis and orbital symptoms. We describe a 15-year-old girl who presented with an acute mass in her medial rectus muscle that was subsequently diagnosed as widely disseminated alveolar rhabdomyosarcoma. To our knowledge, this represents the first reported case in which an enlarged extraocular muscle was the initial manifestation of disseminated alveolar rhabdomyosarcoma.

Incidence of postblepharoplasty orbital hemorrhage and associated visual loss.

PURPOSE: Orbital hemorrhage, especially when associated with visual loss, is a significant complication of cosmetic eyelid surgery. We investigated the incidence of this complication among cases handled by members of the American Society of Ophthalmic Plastic and Reconstructive Surgery. We also reviewed the length of time between surgery and the onset of bleeding and sought any factors that may contribute to these cases. METHODS: A 2-page questionnaire was sent to all American Society of Ophthalmic Plastic and Reconstructive Surgery members. Responses were tabulated as to total numbers of cases performed, the incidence of postoperative orbital hemorrhage, treatments, and incidence of permanent visual loss. Comorbidities were also reviewed. RESULTS: Two hundred thirty-seven responses were received from American Society of Ophthalmic Plastic and Reconstructive Surgery members, collectively representing 269,433 cases. Among these cases, there were 149 orbital hemorrhages, 48 cases associated with temporary visual loss, and 12 cases associated with permanent visual loss. The majority of these cases occurred within the first 3 hours of surgery, and the risk decreased significantly after 24 hours after surgery. Common comorbidities were hypertension, perioperative aspirin use, postoperative vomiting, and increased physical activity. Treatment commonly consisted of wound drainage with cauterization of active bleeders, lateral canthotomy, intravenous steroids, and intraocular pressure-lowering drugs. Orbital decompression was infrequently used; anterior chamber paracentesis was not used. This study is limited by recall biases regarding the number of cases performed by each responding surgeon and the number of relevant cases of orbital hemorrhage. CONCLUSIONS: The incidence of orbital hemorrhage associated with cosmetic eyelid surgery is 0.055% (1:2,000), and orbital hemorrhage with permanent visual loss is 0.0045% (1:22,000) [corrected] Development of orbital hemorrhage is most common within the first 24 hours after surgery, especially within the first 0 to 3 hours, but can occur as late as several days after surgery.

Optic nerve sheath meningiomas and advanced treatment options.

PURPOSE OF REVIEW: Recent trends in the management of optic nerve sheath meningiomas have shifted towards fractionated conformal external beam radiotherapy. The purpose of this paper is to review the current literature on this subject and review the clinical characteristics and natural history of optic nerve sheath meningiomas. RECENT FINDINGS: Articles published within the last 2 years have reported the efficacy of using fractionated radiation therapy alone. A total of 62 patients in three studies have been reported; 40.3% retained stable visual acuity, 41.2% percent had improvement in their vision, and 18.4% percent had a decrease in visual acuity. Median follow-up time ranged from 22 to 51 months in these studies. SUMMARY: Optic nerve sheath meningiomas may be safely managed with fractionated external beam radiotherapy in select patients with possible improvement or stabilization of visual acuity. This represents an enormous improvement in a disease with typically poor visual prognosis.

Porphyria cutanea tarda presenting as cicatricial conjunctivitis.

PURPOSE: To report a case of porphyria cutanea tarda presenting as cicatricial conjunctivitis. DESIGN: Observational study. METHODS: A 31-year-old man presented with bilateral inferior symblepharon, superior tarsal conjunctival scarring and concretions, and recurrent conjunctival and episcleral injection. RESULTS: Four years after initial presentation, the patient developed hepatitis C, and 2 years later blisters on his scalp and hands. Direct immunofluorescence studies of biopsies taken from the palpebral conjunctiva of the right lower lid were negative for cicatricial pemphigoid. A twenty-four hour urine specimen analysis revealed elevated levels of uroporphyrins and polycarboxylated porphyrins, confirming the diagnosis of porphyria cutanea tarda. The patient was treated with repeated phlebotomies and oral hydroxychloroquine, which resulted in a significant decrease in the skin lesions, conjunctival injection, and concretions under the upper lids. CONCLUSIONS: Cicatricial conjunctivitis may be a manifestation of porphyria cutanea tarda.