Immunohistochemical localization of NAD(P)H:quinone oxidoreductase in conjunctival melanomas and primary acquired melanosis.

PURPOSE: Mitomycin C has been used in the treatment of primary acquired melanosis and melanomas of the conjunctiva. Because there is increasing evidence that NAD(P)H:quinone oxidoreductase (EC 1.6.99.2, NQO1) or DT-diaphorase plays an important role in the bioactivation of mitomycin C, we examined pathologic specimens of these tumors for NQO1 by immunohistochemistry. METHODS: Formalin-fixed, paraffin-embedded sections with histologic diagnoses of primary acquired melanosis or conjunctival melanomas were obtained from the Eye Pathology Laboratory, University of Colorado Health Sciences Center. Detection of NQO1 in tissues was performed using standard immunohistochemical techniques with monoclonal antibodies against NQO1 and immunoperoxidase staining. Samples were examined by two independent reviewers and NQO1 staining was graded from 0 (no staining) to 3+ (intense staining). RESULTS: Eleven of 11 melanomas (95% confidence interval, 72% to 100%) and three of three lesions with primary acquired melanosis with atypia stained positively for NQO1. In the melanomas, staining was relatively uniform, while in primary acquired melanosis there was cell-to-cell variability in the staining. CONCLUSIONS: NQO1 was detected by immunohistochemistry in every examined section of primary acquired melanosis and melanoma of the conjunctiva, suggesting that NQO1 may play a role in the bioactivation of mitomycin C in these tumors.

Immunohistochemical localization of NQO1 in epithelial dysplasia and neoplasia and in donor eyes.

PURPOSE: To examine the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase), a potential bioactivating enzyme for mitomycin C in corneal and conjunctival epithelial dysplasia and neoplasia and in normal tissues from human donor eyes, by immunohistochemistry. METHODS: Formalin-fixed, paraffin-embedded sections of human donor eyes and tissue sections with histologic diagnoses of corneal and conjunctival epithelial dysplasia and neoplasia from the Eye Pathology Laboratory, University of Colorado Health Sciences Center were analyzed. Detection of NQO1 in tissues was performed using standard immunohistochemical techniques with monoclonal antibodies against NQO1 and immunoperoxidase staining. RESULTS: All 20 tumors stained positive for NQO1. In seven eyes from four donors, positive staining for NQO1 was detected in all epithelial and endothelial layers, in fibroblasts, in all retinal layers except the photoreceptor outer segments, and in the fascicles and arachnoid of the optic nerve. Only minimal staining was detected in the photoreceptor outer segments and the optic nerve pia and dura. Immunostaining was markedly reduced in all tissues in both eyes from donor 5. Genetic analysis confirmed that this individual was homozygous for a polymorphism in NQO1 (NQO1*2). CONCLUSIONS: NQO1 was detected by immunohistochemistry in every examined section of corneal and conjunctival epithelial dysplasia and neoplasia, suggesting that NQO1 may play a role in the bioactivation of mitomycin C in these tumors. However, the presence of NQO1 in the corneal, conjunctival, and ciliary epithelium; the retinas; and the optic nerves of donor eyes may indicate the potential for mitomycin C toxicity, particularly at higher doses.

Acute unilateral corneal immunoprotein deposition in IgM monoclonal gammopathy.

A healthy 43-year-old officer of a merchant ship at sea developed pain, redness, and photophobia in his right eye. During the next 2 weeks, he noted the presence of a band of opacity spreading from his temporal limbus toward his central cornea. His episcleral vessels were engorged in a distribution contiguous with the peripheral, sectorial, fleck-like corneal opacities. The opacity had progressed during topical and systemic antibiotic therapy, but halted with use of topical corticosteroids. Systemic evaluation showed mild IgM monoclonal gammopathy. Transmission electron microscopy of a corneal biopsy specimen revealed electron-dense fibrils identified as immunoprotein. To our knowledge, this is the first report of a case of acute unilateral deposition of corneal immunoprotein in a patient with monoclonal gammopathy. Clinicians should begin with a broad differential diagnosis when evaluating patients with corneal opacity.

A porcine model predicts that a can-opener capsulotomy can be done safely in pediatric patients.

PURPOSE: The purpose of this study was to compare the strength and safety of a continuous circular capsulorhexis (CCC) with a can-opener capsulotomy (COC) in a porcine model that closely resembles the high elasticity of the human pediatric lens capsule. METHODS: COCs (N = 47) and CCCs (N = 102) were performed inside the anterior chamber of fresh pig eyes, and any uncontrolled tears were noted. The circumference of the initial opening was measured in 18 COCs and 13 CCCs. After the opening was stretched to the point of rupture, the circumference was measured again. The ratio of the circumference at rupture to the initial circumference, minus one, was used as a measure of the maximal capsular strain. RESULTS: The can-opener technique produced a smooth round opening. One of the COCs (2.1%) and 23 of the CCCs (22.5%) had uncontrolled tears (chi2, P<.001). The mean maximal strain for COCs was 46.7% (SE, 8.3%) and for the CCCs, 47.7% (SE, 9.9%). This difference was statistically not significant (P = .93 by Student's t test). CONCLUSIONS: The porcine capsule is more reliably opened with fewer uncontrolled tears by a COC than by a CCC. The porcine model predicts that pediatric capsules can be opened safely with a COC.

Single-pass imaging through a thick dynamic distorter using four-wave mixing.

We have reconstructed images after a single pass through a thick, turbulent aberrator. The reconstructed image's resolution was independent of the presence, severity, and length of a hot-air aberrator (at least 50 times the collecting optics' depth of field). The slowly responding four-wave mixing medium, fluorescein-doped boric acid glass, averaged out rapidly varying intensity apodizations, which would otherwise degrade the reconstructed image quality.

Effects of thick aberrators in one-way imaging schemes.

The ability of one-way imaging schemes to correct for the effects of thick aberrators is examined. These schemes correct an image for the influence of an intervening aberrator in a single pass. Single-pass image correction is observed for thick aberrators that change in times that are short compared with the nonlinear response time of the four-wave mixing material. Image degradation is observed for static aberrators.

Correction of thermal blooming by optical phase conjugation.

We have observed accurate correction of laser-induced thermal blooming by optical phase conjugation. The thermal blooming produced up to a 36-fold increase in the far-field spot diameter and up to a 60-fold decrease in the far-field peak intensity. Stimulated Brillouin scattering was used as the phase-conjugate mirror with a reflectivity of 35% to 65%. A previously published theory regarding phase-conjugate correction of intensity-dependent aberrations suggested that nonunity reflectivity would adversely affect the phase conjugate's ability to compensate for thermal blooming. We found no evidence of this being the case.

Theory of thermal blooming correction by phase conjugation.

We predict accurate correction of thermal blooming by phase conjugation, for the case of a nonunity-magnitude reflection coefficient, over a wide range of easily realized experimental conditions. Diffusion relaxes a thermal grating that would otherwise spoil phase-conjugate correction. Phase conjugation is predicted to correct thermal blooming caused by continuous-wave lasers, collimated or loosely focused lasers, pulsed lasers blooming in gases, and broadband lasers.

Effect of focal intensity on stimulated-Brillouin-scattering reflectivity and fidelity.

We have measured the reflectivity and phase-conjugate fidelity of stimulated Brillouin scattering in hexane while varying the pump power and aberration. By directly measuring the reduction in focal intensity that is due to aberrations, we found that the reflectivity and the fidelity depend solely on the focal intensity. We were able to vary the strength of aberration, producing up to a factor-of-30 reduction in focal intensity. The reflectivity and fidelity decreased monotonically with decreasing focal intensity. There was no minimum amount of aberration required for accurate wave-front reversal, and the maximum amount was the aberration that reduced intensity to near threshold.

Variable phase grating optical aberrator.

We have developed and analyzed a heated laminar airflow device which introduces easily varied aberrations into optical beam trains. The aberrator produced nearly sinusoidal optical path differences of modulation depth 0 to 2lambda (peak to valley) at a 355-nm wavelength and a spatial frequency of ~2 cycles/cm. The phase modulation was measured via lateral shearing interferometry and agreed with a sinusoidal near field phase model to ~10%. The far field intensity profile was in qualitative agreement with the theory of focused sinusoidal phase gratings.