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Objective To analyze the clinical profiles, histopathologic features, and Mycobacterium tuberculosis polymerase chain reaction testing in patients with ocular tuberculosis. Design Retrospective case series. Participants Forty-two patients. Methods This retrospective study was approved by the Armed Forces Institute of Pathology (AFIP) Institutional Review Board. The AFIP data banks were screened for cases with diagnosis of ocular tuberculosis using key words such as mycobacterium; tuberculosis; and acid-fast bacilli. Files and slides stained with hematoxylin–eosin and acid-fast staining were reviewed by the Division of Ocular Pathology and by the Infectious Diseases and Parasitic Diseases Pathology Branches. When available; blocks and unstained slides were sent to the Doheny Eye Institute; Los Angeles; California; for quantitative polymerase chain reaction (qPCR) analysis to detect Mycobacterium tuberculosis-specific DNA. Main Outcome Measures Tuberculin skin test (TST) results, as well as the chest radiograph results, were recorded. When acid-fast bacilli were identified in tissue, their locations—ocular or extraocular sites—were recorded. Emphasis was placed on lymph node involvement and any systemic diseases. Results In the histopathologic specimens, microscopy revealed a paucity of organisms, and often there were only 1 or 2 organisms associated with or near a giant cell or near an area of necrosis. The qPCR analysis was performed on 6 biopsy specimens. These specimens showed necrotizing granulomatous inflammation from 6 different patients; 3 had positive qPCR results. In 2 of the 3 cases with positive qPCR results, acid-fast bacilli were not found in the tissue sections. In 17 patients, TST results were available; 10 had positive results (60%) and 7 had negative results (40%). Fourteen chest radiograph results were submitted, and 8 (57%) of 14 patients had normal chest films. Conclusions This study suggests that in dealing with those populations at increased risk of tuberculosis (e.g., immigrants from endemic areas and human immunodeficiency virus-infected patients) or patients receiving biologic therapy, the ophthalmologist should endeavor to entertain this diagnosis and to rely on the support of infectious disease specialists and pulmonologists to help solidify the diagnosis, because the current methods for the diagnosis have limited sensitivity. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To evaluate the immunohistochemical profiles of the abnormal endothelial cells of posterior polymorphous dystrophy (PPMD) and congenital hereditary endothelial dystrophy (CHED).Formalin-fixed, paraffin-embedded sections of seven corneas with the diagnosis of PPMD (seven patients), six corneas with the diagnosis of CHED (four patients), and five control corneas were stained with hematoxylin-eosin. Adjacent histologic sections were stained with monoclonal antibodies that react with pancytokeratin, AE1/AE3, cytokeratin (CK) 7, CK 20, CAM 5.2, and epithelial membrane antigen. The immunoreactivity of the corneal endothelium was assessed by light microscopy.The endothelial cells stained positive for pancytokeratin and CK 7 in seven of seven corneas of patients with PPMD and five of six corneas of patients with CHED; variable positivity was seen to AE1, AE3, and CAM 5.2. The endothelium was uniformly negative to staining by CK 20. The epithelium stained positive with pancytokeratin, AE1, and AE3. All control corneas were negative for pancytokeratin, CK 7, and CK 20.The abnormal endothelium in both PPMD and CHED expresses similar CKs, including CK 7, which is not present in normal endothelium or surface epithelium. This may indicate a shared developmental abnormality in these conditions, as previously suggested by ultrastructural studies and genetic mapping.

Purpose: To study the histopathologic features of the Mueller muscle in chronic eyelid retraction caused by thyroid-associated orbitopathy. To investigate if the degree of eyelid retraction correlates with any histopathologic finding. Methods: A prospective case series of 23 consecutive patients with thyroid-associated orbitopathy was studied. Specimens were obtained during a standard muellerectomy. Formalin-preserved specimens were studied with the use of hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, and Giemsa stains. Immunostaining against leukocyte common antigen, L26, CD3, and KP-1 was performed. Three control specimens were also evaluated in a similar fashion. Fresh tissue was placed in cold glutaraldehyde overnight, postfixed, dehydrated, and infiltrated with epoxy resin. Silver (70 nm) sections were cut and stained with uranyl acetate and lead citrate for electron microscopic examination. Results: On light microscopy, fibrosis and mast cell infiltration was present in all 23 specimens. Fat infiltration was noted in 16 of 23 specimens and did not correlate with increasing age of the patient. Interstitial edema and lymphocytic infiltration were not observed. On immunohistochemistry, leukocyte common antigen was positive, confirming the presence of inflammation. L26, CD3, and KP1 were negative. Electron microscopy demonstrated fibrosis, mast cells, and abundant contracting Mueller cells. The degree of clinical retraction in millimeters did not correlate with fibrosis, inflammation, or fat infiltration. The control specimens demonstrated rare fat and mast cell infiltration and no fibrosis. Conclusions: Contrary to previous reports, the Mueller muscle is involved in the inflammation and fibrosis that characterizes thyroid-associated orbitopathy. The Mueller muscle is grossly enlarged. On histopathologic inspection, fibrosis, fatty infiltration, and increased mast cell presence accompany focal atrophy of the Mueller muscle. In concordance with prior descriptions, many Mueller cells are in an actively contracting state on electron microscopy.

Anaplastic large cell lymphoma (ALCL) positive for the cell marker Ki-1/CD30 is a recently recognized high grade lymphoma. The authors present a case of a three-year-old female child with a rapidly growing sino-orbital lesion with central nervous system extension, suggestive of rhabdomyosarcoma. The child presented a clinical challenge for prompt diagnosis and treatment.Histologically, the unusual tumor showed a mixture of large malignant lymphocytes and histiocytes. Immunohistochemically, the malignant lymphocytes showed positive reactivity to LCA, Ki-1, CD3, UCHL-1. The histiocytes were positive for KP-1 and lysozyme.There was complete resolution of the lymphoma. To the authors' knowledge, this is the first case of Ki-1+ ALCL lymphoma involving the orbit of a child.

A 75-year-old man developed apparent acute left-sided orbital cellulitis over a three-day period. The vision in the left eye had gradually deteriorated to no light perception over four years. A superonasal epibulbar mass on clinical examination corresponded to the orbital computed tomographic finding of a soft-tissue density that extended through a large scleral defect. Biopsy of the mass was interpreted as consistent with malignant melanoma of the ciliary body with extrascleral extension. Because of gross proptosis due to extrascleral extension of the 'tumor' and persistent pain, a left orbital exenteration was performed. Pathologic examination revealed a partially necrotic tumor that filled the eye and extended through a large scleral defect into the orbit. Polygonal epithelioid and tumor spindle cells with marked nuclear pleomorphism were negative for immunohistologic markers for HMG-45 and S-100 protein and were surrounded by a basement membrane consistent with carcinoma of the nonpigmented ciliary bo...

The clinical and pathological findings in a five month-old black male infant with an orbital lesion are reported. By light microscopy, immunohistochemistry, and electron microscopy the tumor was diagnosed as juvenile xanthogranuloma. Touton giant cells were rare and only two were found when serial sections were made. To the best of the authors' knowledge, this represents the eighth case reported in the English literature.

We describe the clinical and histologic features of the first case, to our knowledge, of hemangioblastoma of the orbit arising from an extraocular muscle. We examined a 73-year-old woman with conjunctival injection, 2 mm of proptosis, and limitation of abduction of the right eye. A medial-lateral orbitotomy was used to approach the medial rectus enlargement noted on orbital imaging. Histopathologic examination with light microscopy and immunohistochemistry demonstrated the characteristic findings of a hemangioblastoma.

To report the clinical and histopathologic findings of an unusual keratopathy, which may represent a new corneal dystrophy in a patient with Alport syndrome (ATS).A 59-year-old woman with longstanding diagnosis of autosomal recessive ATS was evaluated for progressively decreasing vision in the left eye. She had anterior lenticonus and cataract and central corneal stromal opacification with significant thinning and flattening bilaterally. She underwent penetrating keratoplasty and cataract extraction with posterior chamber intraocular lens implantation. We describe the light microscopic and ultrastructural findings from the cornea.Histopathology of the corneal button revealed marked stromal thinning with decreased keratocytes. The endothelial cells were attenuated and focally lost. Immunohistochemical stains for cytokeratin were positive, findings consistent with posterior polymorphous dystrophy (PPMD). Transmission electron microscopy showed necrosis and a marked loss of keratocytes. Multilayering of the endothelium was consistent with PPMD, but mature desmosomes and microvilli were absent. In vivo confocal microscopy on the fellow eye showed linear hyporeflective bands at the level of Descemet's membrane consistent with PPMD. In addition, there were fine linear changes in the deep stroma and diffuse hyperreflectivity of the mid and superficial stroma with lack of identifiable keratocytes throughout.We believe this to be the first reported case to demonstrate some histopathologic features of PPMD in ATS. However, the clinical, histopathologic, and ultrastructural characteristics are not typical of PPMD. This may represent a new phenotypic expression of PPMD or may be a distinct clinicopathologic dystrophy associated with ATS.

Juvenile or infantile xanthogranuloma is a known entity with dermatologic, ocular and systemic involvement. The orbital form is quite rare and is usually associated with other systemic manifestations. Isolated bilateral orbital involvement is known to occur in adults in association with generalized bone involvement and other organ systems as part of the Erdheim-Chester disease syndrome. Primary adult onset bilateral orbital xanthogranuloma not associated with other organ system involvement or dermatologic manifestations, is unusual and should be distinguished from other chronic orbital disorders, such as inflammatory pseudotumor, low grade lymphoma, and infectious orbitopathies. The authors present a case of primary adult onset bilateral orbital xanthogranuloma in a 38-year-old female with painless, progressive bilateral proptosis of 16 years' duration. To our knowledge this is the first case of its kind reported in the ophthalmic literature.

A 75-year-old woman developed acute loss of vision in the OD, ipsilateral periocular pain, an afferent pupillary defect, sectoral optic disc edema, and later ipsilateral proptosis and an intraconal mass. She denied any symptoms of temporal arteritis, and a sedimentation rate was normal. Orbital biopsy demonstrated chronic granulomatous inflammation with perivasculitis. A temporal artery biopsy disclosed findings consistent with temporal arteritis. Following 2000 cGy of external beam radiation, her visual function and orbitopathy completely resolved. This unusual presentation of orbital inflammation in association with temporal arteritis demonstrates that pathologic findings of temporal arteritis may be clinically nonspecific and that external beam radiation may be an effective therapy in this setting.

Amyloid deposition in the iris is rare, scanty and associated with systemic disease. We present a case of isolated localized heavy amyloid infiltration of the iris and describe a new hillock-pattern feature visualized using scanning electron microscopy.

Objective Recent studies indicate that WT1 and Bcl2 protein are detected in melanocytic lesions of the skin. We examined, for the first time, WT1 and Bcl2 expression in a variety of conjunctival melanocytic lesions to evaluate their diagnostic utility compared with other melanocytic markers. Methods Protein expression and localization of WT1 and Bcl2 were studied by means of immunolabeling and semiquantification in 123 conjunctival melanocytic lesions (71 benign nevi, 21 atypical nevi, 11 primary acquired melanosis, and 20 malignant melanomas). Ancillary immunohistochemical studies were performed with Bcl2, S100, HMB45, and Melan A antibodies. Results WT1 showed a graded increase in expression in lesions with increasing atypia. Higher mean numbers of WT1 -positive cells correlated with increasing atypia in melanocytes. In all cases, Bcl2 expression was positive and more robust than was S100, HMB45, or Melan A expression. WT1 and HMB45 frequently showed diffuse and strong staining in atypical nevi, primary acquired melanosis with atypia, and malignant melanomas compared with benign lesions. Conclusions Bcl2 is a highly sensitive immunohistochemical marker for melanocytic tumors of the conjunctiva; HMB45 and WT1 staining distinguishes benign from malignant lesions. Clinical Relevance Our results show that HMB45 and WT1 immunolabeling is helpful in the evaluation of conjunctival melanocytic lesions. Accordingly, we recommend the development of an immunohistochemical panel to classify these lesions.

Keratectasia remains one of the most troublesome complications that can arise after laser in situ keratomileusis (LASIK). Patients with this complication present with an increase in myopia and astigmatism, loss of uncorrected visual acuity, and often a loss of best-corrected visual acuity1-3 due to progressive corneal steepening that takes place centrally or inferiorly.4-6 Ectatic changes can occur as early as 1 week after LASIK,7 or they can be delayed up to several years after the initial procedure.8,9 In many cases, penetrating keratoplasty is eventually performed to manage this complication. The incidence of keratectasia after LASIK has been estimated to be 0.04% to 0.6%3,10,11; however, accurate data based on large-scale clinical studies are not available.1,5,12-14 Although a number of clinical risk factors have been reported,2,5-9,13-17 the mechanisms of post-LASIK keratectasia remain unclear. Studies of the histologic changes in post-LASIK keratectasia have demonstrated variable degrees of corneal thinning in the stromal bed and the flap. Although disruption in the Bowman layer typically observed in keratoconus has not been shown in most cases of post-LASIK keratectasia,2,8,18-20 other pathologic findings, such as macrostriae in the stromal bed, thinning of the stromal collagen lamellae, minimal scarring at the flap-stromal bed interface and lack of inflammation, and the presence of an iron ring around the steepening, have been reported.2,16,18-23 An immunohistochemical study24 on wound healing in ectatic corneas after LASIK also reported no scar tissue formation, indicated by a lack of collagen type III expression, even at the flapstromal bed interface. Keratectasia after LASIK shares similar topographic and clinical characteristics with keratoconus, a noninflammatory disease characterized by thinning of the corneal stroma, defects in the Bowman layer, and the eventual protrusion of the central cornea.25-28 Although some of the keratoconus-like histologic changes have been detected in post-LASIK keratectasia, the biochemical abnormalities found in keratoconus have not been studied in keratectasia. These biochemical alterations include decreased expression of the protease inhibitor α1-proteinase inhibitor (α1-PI) and upregulation of transcription factor Sp1.29-31 In addition, matrix metalloproteinases (MMPs), a group of enzymes that are involved in tissue remodeling, have recently been examined in keratectasia. Studies have detected MMP-3 in rare keratocytes, and MMP-10 expression was elevated in the epithelium of ectatic corneas.32 The MMP expression patterns in keratoconus remain controversial, although over-expression of MMP-1 and MMP-2 has been recently reported in keratoconus corneas.33,34 In addition, MMPs have been implicated in various other corneal conditions, including wound repair and healing, ulcerations, and diabetic corneas.35 In this study, we examined the histopathologic and biochemical characteristics of keratectasia after LASIK using light microscopy and transmission electron microscopy (TEM). Immunohistochemical analysis was also performed with antibodies against α1-PI and transcription factor Sp1. In addition, immunolocalization of major members of the MMP family, MMP-1, MMP-2, and MMP-3, was performed to determine if an MMP-mediated degradation process was involved in keratectasia after LASIK.

PURPOSE Retrocorneal membranes (RCMs) are sometimes present after perforating corneal injury, including failed corneal grafts. This study was performed to understand the origin and cellular composition of these RCMs. METHODS Eleven cases of fibrous RCM associated with perforating injury and ulceration were studied by light and electron microscopy. Monoclonal antibodies against vimentin, actin, and alpha-smooth muscle actin (SMA) were used for immunohistochemical analysis. RESULTS Retrocorneal membranes varied in thickness, extent, and cellularity. There was invariably a direct connection between RCM and wound scar through a gap in Descemet's membrane. Eight RCM and three scars of perforating wounds showed actin- or SMA-positive, vimentin-positive, spindle-shaped cells consistent with myofibroblasts. Electron microscopy showed fibroblasts and myofibroblasts in RCM. Descemet's membrane was often wrinkled in proximity to RCM with myofibroblasts. CONCLUSIONS The scar tissue in corneal wounds is an apparent source of RCM components after perforating corneal injury, extending through gaps in Descemet's membrane. Contractile myofibroblasts are present in some RCMs and may be responsible for wrinkling of Descemet's membrane.