Mark W. Scroggs

Clinical and Histopathologic Observations Concerning Hypotony After Trabeculectomy with Adjunctive Mitomycin C

Prolonged hypotony-induced maculopathy is a serious complication of trabeculectomy with adjunctive mitomycin C. We performed trabeculectomies with intraoperative mitomycin C on 59 eyes of 52 consecutive patients. Exposure time to mitomycin C was five minutes in the first seven patients, two of whom had prolonged hypotony-induced maculopathy. One of these required surgical revision of the filtering procedure. Light and electron microscopic study of the excised, avascular bleb disclosed an irregular epithelium and largely acellular subepithelium of loosely arranged connective tissue. In the remaining 52 eyes, the exposure time to mitomycin C was titrated between two and five minutes according to each patients risk for failure of filtration from excessive fibrosis. Four additional cases of prolonged hypotony-induced maculopathy occurred among these 52 cases (7.7%), all of which were in the lower risk groups that received two- or three-minute exposure to mitomycin C. Four procedures failed, requiring further glaucoma surgery, and all of the patients were in the higher risk groups, receiving three- to five-minute exposures. Our titration of the exposure time to mitomycin C may have reduced, but did not eliminate, the risk fo prolonged hypotony-induced maculopathy, and further study is needed to establish the optimum protocol for the use of this drug as an adjunct to trabeculectomy.

Pulmonary carcinomas with a sarcomatoid element: An immunocytochemical and ultrastructural analysis

Eight primary carcinomas of the lung with a prominent spindle-cell sarcomatoid component were studied by immunocytochemical staining and electron microscopy. The eight tumors were indistinguishable by conventional light microscopy, with the exception of one unusual neoplasm that followed multiple pathways of differentiation with elements of squamous cell carcinoma, rhabdomyosarcoma, chondrosarcoma, and an undifferentiated spindle-cell population. Reticulin fiber production by individual spindle cells and a sharp demarcation of the carcinomatous and sarcomatoid domains by light microscopy were not useful differentiating features. Three of the eight tumors exhibited keratin expression in both the carcinomatous and spindle-cell components. Both immunocytochemical and electron microscopic analyses were required to detect epithelial differentiation, as in one case keratin was identified only by immunocytochemical staining and in another only by ultrastructural examination. Epithelial differentiation was undetectable in the sarcomatoid component of five tumors, and in one case immunoreactive myoglobin was identified in spindle cells; skeletal muscle differentiation was confirmed ultrastructurally. We propose that pulmonary carcinomas exhibiting evidence of epithelial differentiation in a sarcomatoid component be termed spindle-cell carcinomas and that those biphasic tumors exhibiting mesenchymal differentiation into specific tissues, such as neoplastic bone, cartilage, or striated muscle, or lacking epithelial differentiation by light microscopy, immunocytochemistry, and electron microscopy be classified as carcinosarcomas. This distinction may ultimately be unnecessary, because these two tumors may represent different points along a morphologic and biologic continuum.

Histopathological variation in keratoconus.

During examination of 131 penetrating keratoplasty specimens from patients with keratoconus obtained in an 11- year period, we observed two histopathologic variants based on the appearance of Bowmans layer and the corneal epithelium. “Typical” keratoconus specimens had multiple breaks in Bowmans layer and central epithelial thinning, whereas “atypical” corneas lacked breaks in Bowmans layer and had less thinning of the central epithelium. Ninety-five corneas were from patients who underwent grafting in only one eye. Seventy-six (80%) of these corneas were “typical” and 19 corneas (20%) were “atypical” in appearance. Both variants had similar degrees of central stromal thinning. Patients with “typical” and “atypical” corneas differed demographically by race only; 49% of “typical” and 95% of “atypical” corneas were from white individuals. Thirty-six corneas were from 18 patients who underwent bilateral penetrating keratoplasty. The histologic appearance of these corneal pairs was concordant in 13 patients and discordant (one “typical” and one “atypical” cornea) in five patients. Statistical analysis indicated that this distribution is not significantly different from that predicted by chance and suggests that “typical” and “atypical” corneas are manifestations of the same disease process

Associations between cyclosporine therapy and interstitial fibrosis in renal allograft biopsies

No significant difference in any measure of IF was found between all CsA+ vs. CsA- patients, although both groups showed a highly significant increase in IF compared with control pretransplant donor biopsies. Similarly, no differences in tubular changes or the patterns of fibrosis were identified between CsA groups. However, since the mean interval between transplantand biopsy was significantly (p<0.04) greater for the CsA- group, measures of creatining and If were nonrmalized by the time interval between transplant and biopsy, and were stratified into biopsies obtained before or after 6 months posttransplant. By this stratification and normalization, both the baseline creatinine (P<0.01) and the degree of IF as measured by morphometry (P<0.04) were significantly higher in the CsA+ group, but only for biopsies obtained >6 months posttransplant. Evaluation of biopsies > months posttransplant normalized by interval showed no suggested differences between the CsA+ and CsA- groups in terms of creatinine levels or any measure of IF. tubular epithelial changes were not different in the CsA+ and CsA- groups within either period. These results suggest that CsA therapy is not associated with increased interstitial fibrosis in renal allografts prior to 6 months posttransplant, after which there is a signivicant increase in fibrosis relative to patients not receiving CsA.

Evidence that pretransplant donor blood transfusion prevents rat renal allograft dysfunction but not the in situ cellular alloimmune or morphologic manifestations of rejection

The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder strain combination. Indefinite graft survival (mean >63 days) could be induced by DSBT administration alone. In comparison, animals receiving autolgous blood transfusion (ABT) all died within 7 days posttransplantation. As assessed by clearance of inulin and paraaminohippurate, renal allograft function in DSBT-pretreated recipients at 6 days was equivalent to that of isograft recipients, and in contrast to the significant reduction seen in ABT treated rats. Likewise, thromboxane B2 (TXB2) production by ex-vivo-perfused allografts from DSBT-treated recipients was comparable to that of isografts, and significantly lower than that of allografts from ABT-treated rats. A significant inverse correlation was found between renal TXB2 production and inulin clearance. Despite these substantial differences in renal function and eicosanoid metabolism, morphologic evaluation of renal allografts from DSBT-enhanced and ABT-rejecting recipients at comparable time points showed equivalent histologic manifestations of rejection. In addition, immunohistologic labeling of renal allograft sections and fluorescence-activated cell sorter analysis of cells eluted from allografts showed the same phenotype and pattern of infiltrating T cell subsets in both groups. Specific antidonor cytotoxic T lymphocyte precursor (pCTL) frequencies of cells eluted from kidney grafts were equivalent in DSBT and ABT-pretreated animals, and both groups expressed significantly higher (but equivalent) pCTL frequencies in the kidneys than spleens. Comparisons of the lysis of PVG.R1 (RT1.Aa on a PVG background) and ACI targets indicated that cytotoxic responses from effector cells freshly eluted from DSBT and ABT kidneys were primarily directed against allogeneic class I major histocompatibility complex (MHC) specificities, whereas several long term T cell lines generated from 6-day kidney transplants of both groups expressed a predominant W3/25+ (T helper) phenotype and cytotoxic activity against donor specificites other than RT1.Aa class I MHC. Specific antidonor proliferative T lymphocyte (pPTL) precursor frequencies of cells eluted from renal allografts were also equivalent for both DSBT- and ABT-treated recipients, and the range of pPTL frequencies for allograft cell eluates was similar to that in spleens, regardless of the source of the transfusion. Thus, in the rat, the prolonged renal allograft survival seen with DSBT pretreatment is associatated with reduced thromboxane production, and does not appear to involve early depletion of alloreactive cytotoxic or proliferative T cell clones or activity. Moreover, these findings suggest that the presence of significant alloreactive cytotoxic and helper T cell populations within the spleen and allograft itself does not necessarily result in renal transplant dysfunction or rejection.

Corneal argyrosis associated with silver soldering.

We report a patient who developed corneal argyrosis secondary to occupational silver soldering. Clinically, the cornea was notable for a green-brown discoloration localized to Descemets membrane by slit-lamp biomicroscopy. Silver particles were identified within the anterior three eighths of Descemets membrane by light and electron microscopy and energy-dispersive x-ray microanalysis. To our knowledge, the association between corneal argyrosis and silver soldering has not been previously reported.

Peripheral retinal cryotherapy for postvitrectomy diabetic vitreous hemorrhage in phakic eyes

PURPOSE To review the anatomic and visual outcomes of a consecutive series of phakic patients with postoperative diabetic vitreous hemorrhage (PDVH) who underwent revision vitrectomy with peripheral retinal cryotherapy. METHODS We performed a retrospective chart review of consecutive phakic patients who underwent revision vitrectomy for PDVH who also received peripheral retinal cryotherapy. Final corrected visual acuities after revision vitrectomy with peripheral retinal cryotherapy were compared to corrected visual acuities before and at the time of PDVH. Anatomic outcomes such as retinal attachment, vitreous hemorrhage, iris neovascularization, lens opacity, and anterior hyaloidal neovascularization were considered. RESULTS Nineteen (86%) of 22 eyes (21 patients) that underwent revision of vitrectomy and transscleral peripheral retinal cryotherapy for PDVH also received supplementary endolaser photocoagulation in the posterior pole. In 16 eyes (73%), no further vitreous hemorrhaging occurred after this procedure. In six eyes (27%), vitreous hemorrhage recurred after revision of vitrectomy and peripheral retinal cryotherapy but cleared spontaneously in three of these eyes. Of the three eyes with nonclearing recurrent vitreous hemorrhage after revision of vitrectomy and peripheral retinal cryotherapy, the cause for the vitreous hemorrhage was known for two: severe, progressive anterior hyaloidal neovascularization. With a mean follow-up +/- SD of 6.8 +/- 5.1 months (range, 0.5 to 19.5 months), final corrected visual acuity after revision of vitrectomy and peripheral retinal cryotherapy for PDVH improved over preoperative visual acuity (at which time vitreous hemorrhage was present) in 18 eyes (82%) because of removal of vitreous hemorrhage from the visual axis. However, final visual acuity reached or exceeded pre-PDVH visual acuity in only five of the 15 eyes for which pre-PDVH visual acuity was known. CONCLUSION For phakic eyes with nonclearing PDVH, peripheral retinal cryotherapy (often augmented, when possible, by additional posterior pole endolaser photocoagulation) may be used to supplement previous retinal ablative therapy during revision of vitrectomy. This procedure leads to anatomic stabilization and visual improvement in the majority of eyes. Transscleral peripheral retinal cryotherapy is often feasible in situations (such as media opacity) that preclude use of peripheral retinal endolaser or indirect laser photocoagulation.

Eosinophilic intracytoplasmic globules in pulmonary adenocarcinomas: A histochemical, immunohistochemical, and ultrastructural study of six cases

Intracytoplasmic globules have been described in a variety of neoplastic and nonneoplastic conditions, but remain poorly defined. In a review of 100 consecutive cases of lung carcinomas, six cases of mucin-positive adenocarcinoma demonstrated eosinophilic intracytoplasmic globules that ranged in size from less than 1 to 20 mu in diameter. The globules were often located adjacent to areas of tumor necrosis, and occurred either singly or multiply within individual tumor cells. Globules were similar in morphologic appearance to Russell bodies in plasma cells or the eosinophilic globules in hepatocytes of patients with alpha-1-antitrypsin deficiency, but were morphologically distinct from intracytoplasmic mucin vacuoles. The globules were brightly positive with PAS stain with diastase, were brick red with Massons trichrome stain, and showed variably positive staining with Mallorys phosphotungstic acid-hematoxylin and Ziehl-Nielson stains. Immunoperoxidase staining showed slight staining of some globules with albumin, IgG, IgA, and alpha-1-antitrypsin. Ultrastructurally the globules had a homogeneous density and were often associated with profiles of rough endoplasmic reticulum. We suggest that these globules represent secretory glycoprotein accumulated in the cytoplasm of tumor cells in areas of tumor cell injury.

Senile scleral plaques: A histopathologic study using energy-dispersive X-ray microanalysis

The investigators reviewed the pathologic findings of 21 senile scleral plaques in 17 enucleated globes. Eyes were fixed in formalin and routinely processed for light microscopic examination. Two representative calcified scleral plaques were subjected to energy-dispersive x-ray microanalysis. Plaques were located in the sclera just anterior to the insertion of the horizontal rectus muscles. Microscopic examination of the involved sclera disclosed a spectrum of histopathologic changes involving increased hematoxylinophilia of the scleral collagen, decreased stromal cellularity, the presence of scleral fibers with a unique corkscrew appearance, and calcium deposition. The calcified plaques contained calcium phosphate as indicated by histochemical methods and energy-dispersive x-ray microanalysis. Conjunctival elastosis was present in 12 of the 14 eyes in which sufficient conjunctiva was present for histologic evaluation. Accumulated actinic damage from solar irradiation may play a role in the pathogenesis of senile scleral plaques.

Acid Hematin Pigmentation of the Cornea in Stillborn Fetuses

During the postmortem histopathologic evaluation of eyes from stillborn fetuses we noted the presence of a prominent undescribed corneal pigment in 18 of 55 stillborn fetuses. The corneal pigment was frequently associated with documented meconium-stained amniotic fluid, and in no instance was a stained cornea coupled with recorded clear amniotic fluid. Pigmented corneas came from stillborn fetuses with a longer duration of intrauterine death than nonstained corneas. The pigment stained black with the Fontana-Masson stain, was birefringent, and treatment of tissue sections with 5% potassium permanganate and 5% oxalic acid as well as with saturated alcoholic picric acid solution removed the pigment indicating that it is acid hematin. The most likely cause of the acid hematin-stained corneas was tissue acidity created in utero with prolonged intrauterine death.