Lymphoepithelial Carcinoma of the Nasolacrimal Duct: Clinical, Radiologic, and Immunopathologic Features.

Undifferentiated lymphoepithelial carcinoma (exhibiting both begin lymphoid and malignant epithelial components) most commonly arises in the head and neck, especially in the nasopharynx. It may also be encountered in various ocular adnexal sites, including the nasolacrimal duct. A 63-year-old woman developed a swelling in the region of the right lacrimal sac accompanied by epiphora. CT scanning revealed an enlargement of the nasolacrimal duct from the lacrimal sac to the inferior nasal meatus. A biopsy during dacryocystorhinostomy for symptomatic epiphora revealed hypercellular sheets of small lymphocytes which were interpreted as evidence for a chronic dacryocystitis. Two years later the subtotally excised lesion had substantially grown in size. Repeat CT scans demonstrated an inferonasal anterior orbital mass with further enlargement of the nasolacrimal duct with a solid mass in its lumen, and bone erosion. The biopsy combined a rich background of lymphocytes within which were clusters of undifferentiated carcinoma cells that were cytokeratin and p63 positive. Critical review of the earlier biopsy led to the detection of the same cells, but in smaller numbers, that had been overlooked. An awareness of the possibility of lymphoepithelial carcinoma of the lacrimal sac/duct should improve diagnostic accuracy with the aid of immunohistochemistry. Radiation therapy is often successful in managing this highly sensitive malignant tumor.

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.

Age- and fatigue-related markers of human faces: an eye-tracking study.

PURPOSE: To investigate the facial cues that are used when making judgments about how old or tired a face appears. DESIGN: Experimental study. PARTICIPANTS: Forty-seven subjects: 15 male and 32 female participants, ranging from age 18 to 30 years. METHODS: Forty-eight full-face digital images of "normal-appearing" patients were collected and uploaded to an eye-tracking system. We used an Applied Science Laboratories (Bedford, MA) Eye Tracker device associated with gaze-tracking software to record and calculate the gaze and fixation of the participants' left eye as they viewed images on a computer screen. After seeing each picture, participants were asked to assess the age of the face in the picture by making a selection on a rating scale divided into 5-year intervals; for fatigue judgments we used a rating scale from 1 (not tired) to 7 (most tired). MAIN OUTCOME MEASURES: The main outcome measure was gaze fixation, as assessed by tracking the eye movements of participants as they viewed full-face digital pictures. RESULTS: For fatigue judgments, participants spent the most time looking at the eye region (31.81%), then the forehead and the nose regions (14.99% and 14.12%, respectively); in the eye region, participants looked most at the brows (13.1%) and lower lids (9.4%). Participants spent more time looking at the cheeks on faces they rated as least tired than they did on those they rated as most tired (t = 2.079, P<0.05). For age judgments, the eye region (27.22%) and then the forehead (15.71%) and the nose (14.30%) had the highest frequencies of interest; in the eye region, the brows and lower lids also had the highest frequencies of interest (11.40% and 8.90%, respectively). Participants looked more at the brows (t = -2.63, P<0.05) and glabella (t = -3.28, P<0.01) in those faces they rated as looking the oldest. CONCLUSIONS: This study supports the hypothesis that age and fatigue judgments are related to preferential attention toward the eye region. Consequently, these results suggest that aesthetic or functional surgery to the eye region may be one of the most effective interventions in enhancing the appearance of an individual. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

In the eye of the beholder--skin rejuvenation using a light-emitting diode photomodulation device.

BACKGROUND: A light-emitting diode (LED) photomodulation system can produce pulses of amber light expected to induce structural skin changes and reverse the effects of photoaging. OBJECTIVE: To reproduce the encouraging results already published. METHODS AND MATERIALS: Facial skin was exposed to pulses of 588+/-10-nm-wavelength light from a photomodulation device for 40 seconds once a week for 8 weeks. Photographs, clinical assessment, and a subjective questionnaire were taken at baseline, at the last follow-up, and 1 month after that. Thirty-six patients' pre- and post-treatment photos were arbitrarily scrambled, and 30 independent blinded observers were asked to pick the post-treatment photo. Two time-point comparisons were evaluated. RESULTS: For every facial characteristic studied and for both time-point comparisons, patients reported highly statistically significant improvements. In extremely sharp contrast, neither the physician's assessment nor the independent observers' evaluation indicated any improvement. CONCLUSION: Although subjective findings are comparable between studies, we were unable to reproduce the objective results of efficacy previously reported. Patients genuinely believed that several of their facial features had improved, even though there was no detectable objective change. Our data therefore suggest that the LED photomodulation treatment from the device tested is a placebo.

Myeloid Sarcoma with Megakaryoblastic Differentiation Arising in the Conjunctiva.

An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.

Recognizing the protruding eye.

UNLABELLED: It is currently unknown how much exophthalmos may be noticeable to an observer. The authors determined the threshold for detection of exophthalmos may be 4 millimeters. PURPOSE: To determine the threshold for detection of exophthalmos by an observer. METHODS: The Massachusetts Eye and Ear Infirmary Ophthalmic Plastics imaging database was used to select 28 photographs of patients with unilateral exophthalmos measuring between 1 to 11 mm for the study group and 28 photographs of patients without exophthalmos for the control group. One hundred ophthalmology attendings, residents, medical students, and technicians reviewed each photograph. Participants commented on whether the patient appeared "normal" or "abnormal." RESULTS: Eighty-one percent of the control patients were correctly identified as "normal." In comparison, 60% of patients with 1 mm of exophthalmos (p < 0.001), 53% of patients with 2 mm of exophthalmos (p < 0.001), 46% of patients with 3 mm of exophthalmos (p < 0.001), 35% of patients with 4 mm of exophthalmos (p < 0.001), and 40% of patients with 5 mm of exophthalmos (p < 0.001) were identified as "normal." The vast majority of patients (91.9%, p < 0.001) with 6 mm of exophthalmos were identified as "abnormal," and almost all patients (97.9%, p < 0.001) with more than 6 mm of exophthalmos were also described as having an "abnormal" appearance. CONCLUSIONS: Greater than half of the patients with 1-2 mm of exophthalmos appear as "normal" as the control patients. In comparison, the majority of patients with 4-5 mm of exophthalmos and nearly all the patients with 6 mm of exophthalmos and greater appear "abnormal." Our data suggests that the point at which exophthalmos becomes clinically perceptible to the majority of observers is 4 mm. There may be patients with 3 mm of exophthalmos and greater with orbital pathology being "missed" on cursory external examinations by general ophthalmologists, optometrists, and general practitioners.

Green bone.

OBJECTIVE: To describe the unusual finding of yellow-green-colored bone during routine orbital surgery, to detail its investigation, and to demonstrate its benign nature. METHODS: When green bone was found, specimens were sent for light and fluorescent microscopy, ultraviolet photography, and spectrophotometry. RESULTS: Yellow-green bone was encountered in 3 patients during orbital tumor excision or orbital fracture repair procedures. The only common cause was prior use of tetracycline during adolescence. All patients had healthy white dentition. In all cases, absence of neoplasia was demonstrated histologically. The bone fluoresced with a bright yellow-green color when exposed to 365-nm ultraviolet light. Histologic analysis demonstrated fluorescence located near the haversian canals. Spectrophotometry revealed absorption at 4 wavelengths specific to tetracycline: 230, 275, 380, and 440 nm. CONCLUSIONS: Fixation of tetracycline and ensuing fluorescence occurs mostly in areas of new bone growth and mineralization. This happens during childhood but also with bone remodeling associated with tumors or fractures. Once mineralized, teeth should therefore not be affected if tetracycline exposure occurs after ages 8 to 10 years. This paucity of external clues can lead to the surprising but innocuous surgical finding of green bone. Careful history and proper investigation can confirm its origin.

Pre-B-cell acute lymphoblastic leukemia presenting as an orbital mass in an 8-month-old.

PURPOSE: To present the case of an 8-month-old girl with undiagnosed pre-B-cell acute lymphoblastic leukemia (ALL) presenting as an orbital mass. DESIGN: Observational case report and literature review. METHODS: Review of clinical history, radiologic findings, histology of cervical lymph node and orbital biopsies, and follow-up. RESULTS: An 8-month-old girl presented with a 2-week history of right-sided tearing, lid swelling, proptosis, and rhinorrhea. A computed tomographic scan of the orbits revealed a homogeneous, retrobulbar orbital mass eroding into the ethmoid sinuses and nasal cavity, as well as cervical lymphadenopathy. Biopsy of the lesion and enlarged lymph node disclosed medium-sized, uniform, cytologically atypical lymphocytes in a starry sky pattern. Immunohistochemical analysis showed reactivity to antibodies against CD-10, CD-19, CD-34, and terminal deoxynucleotidyl transferase. Cytogenetic analysis of the tumor also revealed a gene rearrangement on chromosome 11q23. Based on these findings, the diagnosis of pre-B-cell acute lymphoblastic leukemia was made, and systemic as well as intrathecal chemotherapy was instituted, which resulted in rapid remission of the leukemia. CONCLUSIONS: The initial presentation of ALL as an orbital mass is exceedingly rare. To the best of the authors' knowledge, this is the earliest reported case of pre-B-cell ALL presenting as an orbital lesion.

Orbital decompression as an alternative management strategy for patients with benign tumors located at the orbital apex.

PURPOSE: Tumors located in the intraconal portion of the orbital apex, especially those inferior to the optic nerve, can be difficult to access surgically, carrying a significant risk of ocular morbidity. The purpose of this study was to investigate outcomes in 5 patients with benign-appearing but symptomatic tumors located in the intraconal portion of the orbital apex in which orbital decompression was performed as an alternative management strategy to resection. DESIGN: Retrospective interventional case series. PARTICIPANTS: Five patients were diagnosed with a compressive optic neuropathy secondary to a benign-appearing tumor at the orbital apex. INTERVENTION: Each patient underwent surgical decompression of the affected orbit. None of the patients had the tumor biopsied or resected. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA), pupillary responses, visual fields (VFs), color vision, and orbital imaging. RESULTS: Each of the patients demonstrated improvement in visual function, as measured by VA, VFs, and, in some cases, color vision. One patient required a second orbital decompression for recurrent optic neuropathy 4 years after the initial decompression. Complications included ptosis and enophthalmos in 2 patients and diplopia in the extreme right gaze in 1 patient. CONCLUSIONS: Orbital decompression is a therapeutic option for patients with compressive optic neuropathies from benign orbital apex tumors, offering potential improvement in optic nerve function while sparing morbidity from attempts at surgical resection.

Histologic correlation of in vivo optical coherence tomography images of the human retina.

PURPOSE: To correlate in vivo human retina optical coherence tomography (OCT)3 images with histology. DESIGN: Case series. METHODS: Linear OCT3 scans through the macula and optic nerve were obtained in three eyes of three patients who then underwent exenteration surgery for orbital cancers. OCT3 images were then correlated with histology. RESULTS: On histology, two eyes were normal, and one eye had dry macular degeneration. The plexiform layers on histology correlated with the green/yellow areas on the OCT3 scans, and the nuclear layers correlated with the black areas on the OCT3 scans. CONCLUSIONS: The authors are unaware of previous reports correlating histology to in vivo human retina OCT3 images. Our findings using human eyes are not different from previous animal studies, in that the plexiform layers are optically highly backscattering and the nuclear layers are not.

Obliterative microangiopathy presenting as chronic conjunctivitis in a patient with relapsing polychondritis.

PURPOSE: To report histopathologic findings and treatment of obliterative microangiopathy in a patient with chronic conjunctivitis due to relapsing polychondritis (RP). METHODS: This interventional case report describes a 50-year-old woman with relapsing polychondritis was referred to the Ocular Immunology and Uveitis Service for bilateral tearing due to refractory chronic conjunctivitis. Ocular examination revealed the presence of bilateral follicular conjunctivitis. Conjunctival biopsy of the inferior palpebral conjunctiva was performed, and the histopathologic findings guided the therapeutic intervention. RESULTS: The pathology of the conjunctival biopsy included granulomatous obliterative microangiopathy with numerous eosinophils, plasma cells, lymphocytes, and epithelioid cells in the substantia propia. The chronic conjunctivitis resolved with systemic methotrexate therapy. CONCLUSIONS: Microangiopathy may cause chronic conjunctivitis in patients with RP and may be a harbinger of evolving nonocular problems as a consequence of incomplete control of this autoimmune disorder. Immunomodulatory therapy should be considered in such cases to prevent possible cardiovascular, renal, respiratory, and neurologic complications of vasculitis. Although methotrexate has been used in treatment of RP-related necrotizing scleritis with poor results, it can be sufficient for the conjunctivitis with microangiopathy associated with RP.

Cutaneous melanomas of the eyelid.

Cutaneous eyelid melanomas are very rare lesions. The lentiginous subtypes are the most frequent melanocytic lesions of the eyelid and can be likened to conjunctival melanocytic lesions like PAM, PAM with atypia and conjunctival melanoma. Compared to melanomas elsewhere on the body, eyelid melanomas have special considerations. Eyelid skin is very thin, the mucocutaneous junction at the lid margin can affect prognosis, the lymphatic drainage pattern is very variable and there is an inherent difficulty to excise wide margins without sacrificing important structures. A customized excision approach, using tissue-sparing "Slow-Mohs" technique, is suggested. Sentinel lymph node dissection has an evolving therapeutic role but remains controversial.

Simplified repair of zygomatic fractures through a transconjunctival approach.

OBJECTIVE: To describe a simplified technique of zygomatic fracture repair. DESIGN: Retrospective, noncomparative case series with description of a surgical technique. PARTICIPANTS: Twenty consecutive patients with zygomatic fractures undergoing repair with the described technique. INTERVENTION: Fracture repair was accomplished with a technique that used a T-bar screw for reduction through a transconjunctival approach. MAIN OUTCOME MEASURE: Successful fracture reduction. RESULTS: Twenty patients with zygomatic fractures underwent successful reduction with the simplified technique. No complications were observed. CONCLUSIONS: The use of the T-bar through a transconjunctival approach is a simplified and effective technique for zygomatic fracture repair.

Successful treatment of idiopathic orbital inflammation with mycophenolate mofetil.

PURPOSE: To report our experience with the use of mycophenolate mofetil for treatment of idiopathic orbital inflammation (IOI). DESIGN: Noncomparative interventional case series. METHODS: We reviewed the records of five patients with IOI who were treated with mycophenolate mofetil. The indications for use included recurrent inflammation after other therapies (four patients) and to avoid corticosteroid-induced blood sugar elevation in poorly controlled diabetes mellitus (one patient). Treated patients were followed for a median of 8.5 months (range, 4-30 months) after mycophenolate mofetil therapy was begun. Main outcome measures were response to treatment, treatment-related side effects, drug dosage, previous and final treatment regimens, and discontinuation of systemic corticosteroids. RESULTS: Mycophenolate mofetil therapy was discontinued in one patient because of nausea. Each of the remaining four patients experienced complete resolution of orbital inflammation. Of these, only one patient remains on prednisone, but at a significantly reduced dose (1 mg/d). CONCLUSION: Mycophenolate mofetil therapy resulted in the resolution of inflammation in patients with refractory or corticosteroid-dependent IOI and was used successfully for a first episode of IOI in a patient for whom corticosteroids were contraindicated.

Isolation and characterization of cultured human conjunctival goblet cells.

PURPOSE: To isolate and characterize goblet cells from normal human conjunctival tissue to determine whether epidermal growth factor (EGF) receptors are present and whether EGF can influence goblet cell proliferation. METHODS: Goblet cells were isolated from explant cultures established from normal conjunctival tissue harvested from patients during periocular surgery. The cells were grown in RPMI culture medium supplemented with 10% fetal bovine serum and characterized using morphology, histochemistry, indirect immunofluorescence microscopy, molecular biology, and biochemistry. Proliferation was determined with a MTT proliferation assay after exposing goblet cells, which had been serum deprived for 48 hours, to increasing concentrations of epidermal growth factor (EGF; 0-80 ng/mL) for 24 hours. RESULTS: Goblet cells were isolated from conjunctival explants by scraping nongoblet cells from the culture dish. Human goblet cells exhibited positive reactivity with alcian blue-periodic acid Schiff (PAS) reagent, goblet cell-specific cytokeratin-7, HPA lectin, and MUC5AC, but negative reactivity to the stratified squamous epithelial cell marker, cytokeratin-4. The mRNA for MUC5AC was detected using RT-PCR. The presence of the EGF receptors EGFR, ErbB2, and ErbB3 was confirmed through Western blot analysis of cell lysates. EGF elicited a concentration-dependent increase in goblet cell proliferation of 160% +/- 0.5%, 188% +/- 0.45%, 293% +/- 1.3%, and 220% +/- 0.5% of control values with 10, 20, 40, and 80 ng/mL EGF, respectively. CONCLUSIONS: Human goblet cells that retain characteristics of goblet cells in vivo can be cultured. EGF receptors are present in human goblet cells, and EGF stimulates their proliferation.

Activation of mitogen-activated protein kinase by cholinergic agonists and EGF in human compared with rat cultured conjunctival goblet cells.

PURPOSE: To compare activation of the p42/p44 mitogen-activated protein kinase (MAPK) by cholinergic agonists and epidermal growth factor (EGF) in cultured human and rat goblet cells. METHOD: . Conjunctiva was removed from either humans during ocular surgery or male Sprague-Dawley rats and cultured in RPMI medium. These cells were incubated with the cholinergic agonist carbachol (10(-4) M) or EGF (10(-8) M) for various times. Before stimulation, cells were incubated with the EGF receptor (EGFR) inhibitor, AG1478 (10(-7) M) or the muscarinic M(3) receptor inhibitor, 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride (4-DAMP; 10(-5) M) for 10 minutes. Proteins were analyzed by Western blot analysis, using antibodies specific to phosphorylated (activated) p42/44-MAPK or total p42-MAPK. Immunoreactive bands were quantified, and data were expressed as percentage of increase over basal. RESULTS: Carbachol (10(-4) M) increased MAPK activity in human and rat cultured goblet cells in a time-dependent manner, increasing pMAPK with a maximum at 10 minutes. EGF (10(-8) M) activated MAPK in human and rat goblet cells in a time-dependent manner with a maximum at 5 minutes. Carbachol- and EGF-induced activation of pMAPK was completely inhibited by AG1478 in cultured conjunctival goblet cells from both species. Carbachol-induced MAPK activity was also completely inhibited by 4-DAMP in both species. CONCLUSIONS: In human and rat cultured conjunctival goblet cells, cholinergic agonists and EGF activate MAPK with a similar time dependency, this activation is receptor mediated, and cholinergic agonists transactivate the EGF receptor. Thus, rat cultured conjunctival goblet cells can be used as a model to study human conjunctival goblet cells.

Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome.

OBJECTIVE: To evaluate the distribution and clinical as well as treatment outcome characteristics of idiopathic orbital inflammation with the aim of delineating a more systematic approach to diagnosis and treatment. METHODS: A 10-year retrospective review of patients with idiopathic orbital inflammation treated at one institution. RESULTS: Ninety eyes in 65 patients (22 men and 43 women) were studied. Diagnoses were isolated dacryoadenitis (n = 21), isolated myositis (n = 19), concurrent dacryoadenitis and myositis (n = 5), orbital apex syndrome (n = 6), and idiopathic inflammation involving the preseptal region, supraorbital region, sclera, Tenon capsule, orbital fat, or optic nerve (n = 14). The mean age at presentation was 45 years. Pain and periorbital swelling were the most common clinical features and were observed in 45 (69%) and 49 (75%) patients, respectively. Seventeen patients (26%) had bilateral involvement. Biopsy was performed in 19 patients (29%) with atypical presentations or who failed to respond to the initial therapy. Patients were treated with steroids alone (n = 45), steroids and subsequent radiation therapy (n = 8), steroids and nonsteroidal anti-inflammatory agents (n = 6), nonsteroidal anti-inflammatory agents alone in mild cases (n = 2), and, rarely, radiation therapy without steroids (n = 1) or surgical debulking alone (n = 1). Of 65 patients, 41 (63%) represented treatment successes, with complete symptom relief at the time of the last follow-up, and 24 (37%) represented treatment failures, with partial or no relief of symptoms. Treatment failures were often characterized by recurrence of inflammation after a period of quiescence (58%) and unremitting, recalcitrant inflammation (38%); 1 patient ultimately required an exenteration. CONCLUSION: Systemic steroid with a slow taper has been the established first-line treatment for idiopathic orbital inflammation, but refractory cases accounted for a significant portion of treatment failures in our study, reflecting the need for a more systematic approach to the study of this multifaceted disease and for therapeutic alternatives to systemic steroids.

The evolution of endonasal dacryocystorhinostomy.

Dacryocystorhinostomy is an important treatment in the relief of tearing. Through the years, there have been several advances in this procedure. Once performed only from an external approach, the advent of rigid endoscopes and endoscopic instrumentation has made the endonasal approach a reality. Advantages of the endonasal approach include lack of a cutaneous incision and excellent visualization of intranasal pathology, which is often the cause of dacryocystorhinostomy failure. Preoperative evaluation including a detailed medical history, physical examination with office endoscopy, and imaging, as well as postoperative care are important. Surgical technique with detailed knowledge of intranasal anatomy and meticulous attention to hemostasis are critical. Endonasal laser-assisted dacryocystorhinostomy is also performed today, and special preoperative considerations and key features of the lasers available are important in the selection of a laser for tissue or bone ablation during the procedure. Endoscopic conjunctivodacryocystorhinostomy is performed today, and given the critical nature of proper length and placement of the Jones tube intranasally, provides the significant advantage of intranasal visualization. Endoscopic dacryocystorhinostomy in children is also performed today; however, challenges such as small nasal anatomy and maintenance of the intranasal osteomy postoperatively in a child are significant issues.