N. Grace Lee

Malignant rhabdoid transformation of a longstanding, aggressive, and recurrent orbital angiomyxoma.

A 47-year-old woman presented with a medial orbital tumor initially diagnosed as either a myxoid neurofibroma or myoepithelioma. Over 30 years the tumor recurred seven times and was serially debulked. Careful histopathologic analysis coupled with immunohistochemical studies performed on the last two biopsies established the rare diagnosis of a locally aggressive angiomyxoma (because of its local infiltrative growth) with myofibroblastic features (smooth muscle actin and calponin positivity and desmin negativity). The last recurrence manifested at a shorter interval than the earlier ones, suggesting an accelerating clinical course. By this late stage there was complete blindness, a frozen globe, and extreme, unmeasurable proptosis accompanied by massive chemosis and eyelid fullness. An exenteration was performed, and the orbital contents contained a persistent angiomyxoma, but additionally, another cellular population had emerged-mitotically active cells with a malignant rhabdoid phenotype (round shape, cytoplasmic hyaline/globoid inclusions composed of whorls of compact vimentin filaments as well as epithelial membrane antigen and focal cytokeratin positivity). This is the first orbital case of a rhabdoid transformation of a benign orbital mesenchymal tumor. Shortly after the exenteration, multifocal metastases, notably to the lungs, were found, leading to the introduction of chemotherapy, which was discontinued because of non-responsiveness of the tumor and patient intolerance. After 1 year of follow up, the patient is still alive, but has persistent active disease with widespread metastases and a guarded prognosis.

Epstein-Barr Virus–Positive Polymorphous Lymphoplasmacytic Infiltrate of the Lacrimal Glands in a Patient With Acute Lymphoblastic Leukemia

Author Contributions: Dr Schaal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: All authors. Study supervision: Schaal.

Endogenous panophthalmitis with orbital cellulitis secondary to Escherichia coli

known causative agents of keratoconjunctivitis. AdV is commonly associated with a diffuse epithelial keratopathy, followed by the appearance of subepithelial corneal infiltrates, which may persist for months or years. In contrast, a stromal keratitis is predominantly related to infection with members of the herpesvirus family. In the absence of a history or evidence of a previous herpetic keratitis and an absence of herpes simplex virus 1, 2 in tear samples, it would be unlikely that both patients developed a concomitant herpetic keratitis. Given that AdV was still being shed in the tear film during the most severe period of the keratitis, and the subsequent clearance of the oedema following cessation of AdV shedding, would suggest that the stromal reaction and KPs were due to an immune reaction to virus within the corneal stroma. The onset of the stromal disease, that is, 2-3 weeks, is consistent with the development of an adaptive immune response. Increased activated dendritic cells in the epithelium and stroma is a well-established immune response in AdV keratoconjunctivitis. The increased severity of the stromal oedema and KPs in the second patient possibly reflects an enhanced immune response as a consequence of a previous episode of AdV keratitis. The development of centrally localized stromal oedema and KPs in the presence of coexistent subepithelial infiltrates, has, to our knowledge, not previously been reported in AdV keratoconjunctivitis and although rare should be considered in the differential diagnosis of viral stromal keratitis.

Microdebrider Use in Orbital Surgery

Abstract Purpose: To report the novel use of a sinus microdebrider for the removal of tissue during orbital surgery. Methods: This retrospective study reviewed the logs of 3 surgeons to identify patients who required orbital surgery during which the surgeon chose to use a sinus microdebrider with an open sky technique as a means of removing portions of the orbital tissue. Collected data included patient demographics, clinical examinations, pathologic diagnoses, radiologic studies, operative reports and, when available, photographs and intra-operative video. Results: Three patients were identified as having undergone orbital surgery assisted by the use of a sinus microdebrider. The first patient had an extensive, recurrent left orbital myxoid tumor. Debulking of this gelatinous, infiltrative mass was aided by the combined suction and cutting action of the microdebrider. Two cases involved orbital exenteration for infiltrative sino-orbital fungus infection resulting in a blind eye and frozen globe. Removal of orbital apical tissue during exenteration surgery was facilitated with the microdebrider. Conclusions: The characteristics of the sinus microdebrider make it a useful adjunct for orbital surgery, particularly in situations where tissue may be difficult to grasp and excise. Caution should be exercised whenever using this electrically powered tool due to its potential for rapid tissue destruction. Therefore, the microdebrider should only be used in cases in which there is little risk of damage to essential orbital structures.

Dacryops in the setting of a Boston type II keratoprosthesis.

Dacryops of the lacrimal tissue can develop under diverse circumstances. Recent evidence suggests that scarring or obstruction of the lacrimal ducts may lead to their dilatation and formation of a cystic structure. Patients who undergo repeated orbital surgery may therefore be at greater risk of dacryops formation. In this report, a patient who underwent multiple corneal and glaucoma procedures including Boston type II keratoprosthesis, after acid burns to both eyes, is described. Over time, a fluid-filled collection developed in the lower orbit. On surgical exploration and incision, fluid was drained from a cystic lesion which abutted the lacrimal gland and spanned the upper and lower orbits. The lesion was removed and was proven by histopathology and immunohistochemistry to be dacryops. This is the first known case of dacryops associated with Boston type II keratoprosthesis.

Lymphocyte Expression in Graves Orbitopathy

In keeping with the tradition at the University of Pisa of producing well-conceived and pertinent investigations of Graves orbitopathy (GO), Dottore et al1 are to be commended for their thought-provoking study published in this issue of JAMA Ophthalmology regarding the presence of T and B cells in this perplexing disease. Since the 1980s, the role of T and B cells has been investigated in the orbits of patients with GO.2 It was initially thought that the infiltration was exclusively in the extraocular muscles with minimal involvement in the adipose tissue2; since then, there have been numerous studies demonstrating not only lymphocytes but also macrophages within the orbital fat and perivascular interstitial space of these patients.3 Because of these findings, immunosuppressive agents became a mainstay of treating patients with GO.4 However, it has become evident to clinicians managing the disease that the efficacy of these medications is dramatically higher during the active, inflammatory phase compared with the inactive phase.4 Moreover, there are increasing numbers of patients who are not only refractory to corticosteroids, but also intolerant of longterm corticosteroid use. Hence, the question has been raised whether therapy directed at lymphocytes is optimal for GO. Another perspective of GO research has centered on the orbital fibroblast as the key effector cell, which when stimulated, can differentiate into myofibroblasts and adipocytes and produce glycosaminoglycans in excess.5 This activation occurs by stimulation of autoantigens on the fibroblasts with T cells; hence, lymphocytes play an integral role in perpetuating the deleterious effects of these orbital fibroblasts, and their presence in orbital tissue at different stages of GO may reveal salient information about the timing of treatment. Dottore and colleagues1 shed light on this question of the presence and type of lymphocytes in GO, wherein they describe a correlation between clinical activity score (CAS) and infiltrating orbital lymphocytes in adipose specimens acquired during consecutive orbital decompressions.6 In their article,1 20 orbital specimens from patients with active and inactive GO were assessed with immunohistochemistry, specifically with CD3 (T cell) and CD20 (B cell) markers. The number of cells were counted by a masked pathologist, and a simple linear regression model was developed. The positive correlation between lymphocytes and CAS was analyzed and quantified, demonstrating an increase of 1.52 points in CAS for every 10-fold increase in total number of orbital lymphocytes. The correlation was similar when analyzed separately into T cells and B cells. There was no correlation between lymphocyte number and other clinical characteristics, including thyrotropin receptor antibody levels.6 What is remarkable about this study is the fact that the orbital lymphocytes maintained their effect on CAS when adjusted for other covariates, including smoking and duration of disease, in a multiple linear regression model.6 To our knowledge, this is the first time a correlation has been shown between lymphocytes and CAS that persists in the chronic stage of the disease, which does not corroborate the finding that immunosuppressants are most effective during the early, active phase of the disease. It is a notable and perhaps compounding factor in this study that, in addition to many of the patients being in the chronic phase of GO, most patients (17 of 20 [85%]) were decompressed for “severe, disfiguring proptosis.”1 Hence, this was a subgroup of patients with GO that for unknown reasons had worse or persistent proptosis than their counterparts. The authors propose that it remains to be established whether the chronic changes are due to continued migration of lymphocytes from vessels vs the lymphocytes being trapped and unable to leave the microenvironment of the orbit. These unknown etiologic factors may also influence the severe and sustained proptosis in the study population. Our group has investigated this idea, stemming from the basic question of why the orbit microenvironment is uniquely susceptible to these inflammatory changes in GO, while looking beyond the focus on the orbital fibroblast. Previous investigations have demonstrated that the normal orbit uniquely lacks lymphatics. As such, we investigated the differences in orbital vasculogenesis in acute vs chronic GO and found increased angiogenesis accompanied by an increase in vascular growth factors and receptors in acute GO, as well as an increase in differential expression of lymphatic vessels between the 2 groups. These new vessels that are transiently present in the active stage of GO may be responsible for the migration of inflammatory cells and mediation of orbital edema.6 Why these changes persist more in some orbits than others is still open to discovery. Hence, future studies focused on a variety of factors in the pathogenesis of GO will likely someday lead to a full understanding of this complex cascade. Myriad research is being performed on variables influencing the milieu of the orbit, including gene expression studies to discern upregulation or downregulation of specific genes during the active vs inactive phase of GO.7 Determining how these distinct perspectives of GO research affect one another and fit into the big puzzle is critical. Equally important is elucidating as much information as possible on how each individual component behaves in the environment of GO. Dottore and colleagues1 are to be congratulated for this important study, which demonstrates information that contradicts current thinking and will likely initiate further translational studies wherein histopathological findings can direct a specific treatment paradigm. The world of medicine is rapidly advancing with the new age of targeted molecular therapies for a growing number of conditions. Likewise, the elucidation of the pathophysiology of GO is essential to the development of novel targeted treatments for this disfiguring and potentially blinding disease. Related article Lymphocyte Expression in Graves Orbitopathy Invited Commentary

Orbital exenteration: The 10-year Massachusetts Eye and Ear Infirmary experience

ABSTRACT The authors report their experience with orbital exenteration surgery at one academic institution over a 10-year period and review the literature. This retrospective cohort study monitored outcomes of all patients who underwent orbital exenteration surgery at Massachusetts Eye and Ear Infirmary between January 2003 and January 2013. Patients with no follow-up data or survival data were excluded from the study. The main outcome measures were surgical complications, disease status of surgical margins, need for adjuvant treatment, local recurrence, metastases and survival. 23 patients with malignancy and 2 with mucormycosis met inclusion criteria for the study. Surgical procedures included non-lid sparing total exenteration (44%), lid-sparing total exenteration (32%), non-lid sparing partial exenteration (8%) and lid-sparing partial exenteration (16%). 44% underwent additional extra-orbital procedures. Survival rates were 72% at 1 year, 48% at 3 years, and 37% at 5 years. Of patients with malignancies, 48% had clear margins after exenteration. There was no statistically significant difference in survival between patients with negative surgical margins compared to positive margins (p = 0.12). Mortality was highest in patients with melanoma (85.7%) and lowest in patients with non-squamous cell lid malignancies (0%). Our study suggests that the type of disease has a much greater impact on the survival of patients undergoing exenteration surgery than the type of exenteration surgery or the disease status of surgical margins. Patients with non-squamous cell lid malignancies and localized orbital disease have the best prognosis for tumor eradication from this radical and highly disfiguring surgery.

Response to phenylephrine testing in upper eyelids with ptosis.

OBJECTIVE To evaluate the response of ptotic upper eyelids to topical phenylephrine 10%. METHODS The medical records of patients referred for ptosis evaluation over an 18-month period were retrospectively reviewed. Seventy-seven ptotic upper eyelids with aponeurotic dehiscence in 47 patients were given 1 drop of 10% phenylephrine. Margin-to-reflex distance 1 (MRD1) and levator excursion were recorded and photography of lid height was performed both pre- and 5 minutes post-phenylephrine testing. RESULTS A total of 77 ptotic upper eyelids of 47 patients were included. In 22% of lids, phenylephrine testing produced no response; in 18%, lid elevation of 0.5-1 mm; in 35%, elevation of 1.5-2 mm; and in 25%, elevation of > 2 mm. Subgroup analyses revealed a higher proportion of response in cases of mild to moderate ptosis compared with cases of severe ptosis. The amount of levator function in these cases of aponeurotic dehiscence did not correlate with the amount of response to phenylephrine. CONCLUSIONS A majority of ptotic eyelids, regardless of levator function, responded to topical phenylephrine, which has been demonstrated to be necessary for successful Müllers muscle resection ptosis repair. While the severity of ptosis was linked to eyelid response to phenylephrine, the degree of levator function did not appear to affect an eyelids response to phenylephrine. In this study cohort, phenylephrine was shown to stimulate Müllers muscle contraction independently of levator function.