Kathryn S. Pokorny

Diagnosis and treatment of orbital optic nerve sheath meningioma

BACKGROUND Primary and secondary optic nerve sheath meningiomas (ONSMs) are neoplasms that account for a large proportion of optic nerve and orbital tumors. The diagnosis is not always straightforward and is based on the appropriate clinical findings and neuroimaging. Biopsy or surgical intervention may occasionally be necessary but is associated with significant morbidity. METHODS Issues related to clinical signs and symptoms, diagnosis, natural history, and treatment strategies are reviewed based on a review of published literature. RESULTS Diagnosis is usually based on radiographic and clinical findings. Biopsies are not obtained in most cases, thus adding further to the bias of possible misdiagnosis in all reported case series that do not have the benefit of histopathologic confirmation. Natural history typically shows inexorable progression in most cases, although long periods of stability are occasionally reported. Treatment options include observation, radiation alone, surgery alone, and combined radiation and surgery. The optimum timing of interventional therapy and radiation are evolving. CONCLUSIONS After serial examination documents new decline in acuity and/or visual field, fractionated radiotherapy appears most likely to preserve visual function and is a valid treatment approach for primary orbital ONSM. Tumor enlargement, as determined by serial imaging, may also provide an indication to begin radiotherapy.

Use of Split-Thickness Dermal Graft in the Surgical Treatment of Corneal and Scleral Defects

We used split-thickness dermal grafts for the surgical treatment of corneal and scleral perforations in two patients and obtained excellent results. Patient 1 had severe lye burns and bilateral corneal perforations and Patient 2 had scleromalacia perforans. The dermal graft self-epithelializes and, thus, does not need to be covered by conjunctiva; is supple, without the bulkiness of other materials, particularly cartilage and periosteum; is hearty and flourishes on avascular surfaces such as cornea and sclera; has good tensile strength; and is autogenous.

Diplopia and Strabismus Following Ocular Surgeries

Postoperative diplopia and strabismus may result from a variety of ocular surgical procedures. Common underlying mechanisms include sensory disturbance, scarring, direct extraocular muscle injury, myotoxicity from injections of local anesthesia or antibiotics, and malpositioning of extraocular muscles by implant materials. The most common patterns are vertical and horizontal motility disturbance. Treatment options include prisms, botulinum, occlusion, or surgery.

The role of proliferating cell nuclear antigen (PCNA) in differentiating idiopathic orbital inflammatory disease and lymphoid proliferations

Summary The purpose of the present study was to determine whether proliferating cell nuclear antigen (PCNA), an immunohistochemical marker for a nuclear protein abundant in actively proliferating (dividing) cells, is useful as an aid in differentiating idiopathic orbital inflammatory syndrome (IOIS) from lymphoproliferative lesions (LLs). Records of all patients with IOIS and LLs were studied retrospectively. Tissue biopsy specimens from four patients with IOIS and nine patients with LLs were examined. The diagnosis in each case was based on presenting signs and symptoms, orbital computed tomography (CT) and/or magnetic resonance (MR) scans, histopathologic criteria, and follow-up data consistent with the entity. These findings were correlated with the percentage of B- and T-cells in the lesions as well as with the number of cells that demonstrated staining for PCNA in formalin-fixed tissue. PCNA activity was markedly increased in the higher grade (HG) lymphoma group as compared to that in the low grade (LG) lymphoma and idiopathic inflammatory group. Lymphoma cases showed a significantly increased B-/T-cell ratio compared to IOIS lesions. PCNA activity in conjunction with the ratio of B-/T-cells may be a helpful immunohistologic adjunct for differentiating purely inflammatory lesions of the orbit from lymphoid tumors. Further studies are necessary to compare PCNA activity in fresh frozen tissue with that in formalin-fixed tissue.

Roles of Corneal Epithelial Ion Transport Mechanisms in Mediating Responses to Cytokines and Osmotic Stress

Normal vision depends, in part, on the combined refractive powers of the cornea and crystalline lens to permit adequate focusing of light onto the retina. Such refractive function requires that the cornea remain transparent, a requirement that is met provided that corneal hydration, i.e., deturgescence, is maintained within specific physiological limits. Maintenance of corneal deturgescence is reliant upon coupled ion and fluid transport activities within the epithelial and endothelial layers. Net ion transport activity offsets the natural tendency of the corneal stroma to imbibe fluid from the anterior chamber, thus keeping the cornea transparent (1–5). Although most of the ion transport activity involved in maintaining corneal deturgescence is contingent upon ion transport processes localized in the corneal endothelial layer, corneal epithelial ion transport activity plays a fine-tuning role in maintaining corneal deturgescence during exposure to environmental challenges (6) (Fig. 1). Only under maximally stimulated conditions is the epithelial-side fluid transport rate able to increase sufficiently, i.e., to approximately 25% of the endothelial-side fluid transport rate (7). This realization has prompted a host of studies concentrated on characterizing receptor-mediated regulation of corneal epithelial active ion transport.

Conjunctival scarring after eyelid surgery as first sign of ocular cicatricial pemphigoid.

Diagnosis of ocular cicatricial pemphigoid (OCP), a chronic cicatrizing autoimmune disease of the conjunctiva, may be difficult in the early stages of the disease. We noted abnormal conjunctival scarring in three patients who had undergone eyelid and strabismus surgery, which caused us to suspect OCP. In all three patients who subsequently underwent conjunctival biopsy, immunoglobulin or complement in the basement membrane zone detected by direct immunofluorescence helped establish the diagnosis. Although OCP typically is a disease of the elderly, the three patients in this study were aged <50 years; one patient was 19 years old. The present study demonstrates that a diagnosis of OCP should be considered for patients who develop abnormal conjunctival scarring after eyelid or strabismus surgery.

Potassium-Chloride Cotransporter Mediates Cell Cycle Progression and Proliferation of Human Corneal Epithelial Cells

Epidermal growth factor (EGF)-induced proliferation of corneal epithelial cells contributes to its renewal, which maintains the protective and refractive properties of the cornea. This study characterized in human corneal epithelial cells (HCEC) the role of the potassium–chloride cotransporter (KCC) in mediating (i) EGF-induced mitogen-activated protein kinase (MAPK) pathway activation; (ii) increases in cell cycle progression; and (iii) proliferation. The KCC inhibitor [(dihydroindenyl)oxy] alkanoic acid (DIOA) and KCC activator N-ethylmaleimide (NEM), suppressed and enhanced EGF-induced p44/42MAPK activation, respectively. Such selective modulation was mirrored by corresponding changes in cell proliferation and shifts in cell cycle distribution. DIOA induced a 20% increase in G0/G1-phase cell population, whereas NEM induced a 22% increase in the proportion of cells in the G2/M-phase and accelerated the transition from G0/G1-phase to the S-phase. Associated with these changes, KCC1 content in a plasma membrane enriched fraction increased by 300%. Alterations in regulatory volume capacity were associated with corresponding changes in both KCC1 membrane content and activity. These results indicate that EGF-induced increases in KCC1 activity and content modulate cell volume changes required for (i) activation of the p44/42MAPK signaling pathway, (ii) cell cycle progression, and (iii) increases in cell proliferation.

Histopathology of human keratorefractive lenticules.

Eight human corneal lenticules (three from keratophakia, two from hypermetropic keratomileusis, and three from myopic keratomileusis) were examined by light and electron microscopy. The keratophakic lenticules were removed for optical reasons 3, 3.5, and 6 months after surgery. Microscopically, all displayed hypocellularity, mature collagen fibrils and microfibrils, keratocyte ghosts, and keratocytic debris. The hypermetropic keratomileusis specimens were removed at 13 and 14 months postoperatively, the first because of opacities from enzymatic digestion of the cornea, and the second due to contact lens-induced erosion of Bowmans layer and decreased lacrimal secretion. Ultrastructurally, both lenticules exhibited fractures in Bowmans layer, and the 14-month specimen showed multilayered squamous epithelia. The myopic keratomileusis specimens were removed at 4, 8, and 48 months postoperatively due to opacification of the interface caused by delayed epithelial healing, detergent trauma, and previous epithelization, respectively. Electron microscopy revealed fractures in Bowmans layer, subepithelial fibrocellular growth, sparse keratocyte populations of the anterior stroma, porous collagen bundles, keratocytic debris, and regions of epithelial ingrowth.