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.

Histology of conjunctival vascular endothelium after filtering surgery with mitomycin C in rabbits.

OBJECTIVE: To examine histologic changes in conjunctival vasculature during the first 72 hours following filtering surgery with adjunctive mitomycin C in rabbits. DESIGN: Thirty-six New Zealand white rabbits underwent unilateral posterior lip sclerectomy. In 18 rabbits mitomycin C (0.5 mg/mL) was applied subconjunctivally for 5 minutes. The remaining 18 animals were treated with the phosphate-buffered saline vehicle for 5 minutes. Three rabbits from either group were killed at 0, 4, 12, 24, 48 and 72 hours postoperatively. OUTCOME MEASURES: Degree of vascularity of filtering blebs on gross examination and appearance of conjunctival vascular specimens on light and transmission electron microscopy, as assessed by three masked observers. RESULTS: On gross examination the filtering blebs in the mitomycin C group were slightly less hyperemic than those in the control group at 12, 24 and 48 hours and were markedly less hyperemic at 72 hours. Light microscopy showed tightly packed erythrocytes within the conjunctival vessels of the experimental blebs and an almost total absence of endothelium within many of the vascular channels by 72 hours. Transmission electron microscopy showed focal loss of vascular endothelial cells and thrombus formation in the experimental blebs, as early as 12 hours postoperatively. CONCLUSIONS: Our findings suggest that the decreased vascularity of filtering blebs observed after trabeculectomy with adjunctive mitomycin C is at least partially due to a toxic effect of the agent on the endothelial cells of the conjunctival vessels.

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 patient's 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.

The effect of angiostatic steroids and beta-cyclodextrin tetradecasulfate on corneal neovascularization in the rat.

Folkman and coworkers have described angiostatic steroids that markedly inhibit neovascularization of the rabbit cornea when given topically with beta-cyclodextrin tetradecasulfate (beta-CD), yet have minimal or no glucocorticoid or mineralocorticoid activity. Our objective was to extend these observations to another species, the rat. We induced neovascularization by cauterizing rat corneas with silver nitrate/potassium nitrate; drugs were applied topically four times per day for 4 days in most experiments. Submicron sized emulsions of lipid-soluble dexamethasone and the angiostatic steroids 17 alpha-hydroxyprogesterone (1 or 10 mg ml-1) and cortexolone (1 or 10 mg ml-1) were prepared by lecithin encapsulation of drug microcrystals. The vehicle for water-soluble hydrocortisone 21-phosphate (HCP) +/- beta-CD (Molecusol; Pharmatec, Inc) was 10% Tween 20 in Tris-buffered 0.9% saline. Angiogenesis was significantly inhibited only by 1 mg ml-1 dexamethasone (-63.2% when compared with controls), 0.5 mg ml-1 HCP + 1 mg ml-1 beta-CD (-33.4%), and 1 mg ml-1 HCP (-40.2%). HCP (0.5 mg ml-1) or beta-CD (1 or 2 mg ml-1) alone had no significant effect on neovascularization; the inhibition by 1.0 mg ml-1 HCP was not potentiated by 2 mg ml-1 beta-CD. We also tested HCP and tetrahydro-S (TH-S) using 1.5% hydroxypropyl methylcellulose vehicle and beta-CD from Takeda Chemical Industries, Ltd., to simulate the procedure of Folkman and coworkers.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcific phacolysis.

BACKGROUND AND METHODS: The authors report the clinical and ocular histopathologic findings in three patients with longstanding unilateral post-traumatic blindness. After one or more decades, acute pain associated with conjunctival hyperemia and apparent keratoprecipitates or a hypopyon developed in the affected eye of each individual. Phacoanaphylaxis was diagnosed preoperatively in two patients. RESULTS: Calcified granular lens fragments were dispersed throughout all three eyes. The anterior chamber in all patients contained extracellular calcified lens particles, but only one eye contained conspicuous macrophages. Two eyes showed elevated intraocular pressure (IOP), and in one patient calcified particles extended into a glaucomatous optic nerve head. CONCLUSION: To the authors' knowledge, this is the first report describing a rare condition involving the intraocular dispersal of calcified lens particles after disruption of the lens capsule. The authors have designated this entity as calcific phacolysis.

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 Bowman's layer and the corneal epithelium. "Typical" keratoconus specimens had multiple breaks in Bowman's layer and central epithelial thinning, whereas "atypical" corneas lacked breaks in Bowman's 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.

Successful therapy for trilateral retinoblastoma.

Trilateral retinoblastoma, the intracranial malignancy associated with bilateral retinoblastoma, is an uncommon and clinically aggressive malignancy with a uniformly fatal outcome. Three children with newly diagnosed trilateral retinoblastoma were treated with systemic (cyclophosphamide and vincristine) and intrathecal (methotrexate, hydrocortisone, and cytarabine) chemotherapy, as well as craniospinal irradiation (one patient) in addition to therapy of the eye lesions. All three patients have had partial or complete response of the pineal tumors to chemotherapy, with no active disease eight or more years, 33 or more months, and 12 or more months, respectively, after diagnosis of the lesions.

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 Descemet's membrane by slit-lamp biomicroscopy. Silver particles were identified within the anterior three eighths of Descemet's 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.

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.

The effect of total-body irradiation on corneal neovascularization in the Fischer 344 rat after chemical cauterization.

Previous investigations of corneal neovascularization after irradiation yielded discordant results. Most studies indicated that new blood vessel formation in the cornea is inhibited by irradiation. However, others reported that angiogenesis after corneal cauterization is similar in both irradiated and nonirradiated animals. To assess the effect of total-body irradiation on neovascularization further, the amount of angiogenesis was determined in irradiated rats after chemically induced corneal injury. Corneal tissue was evaluated quantitatively with computerized image analysis 2, 3, or 4 days postcautery in rats perfused with India ink and gelatin immediately after death. The rats were exposed to a single dose (9 Gy) of total-body irradiation 6 days before corneal cauterization. In both the nonirradiated and irradiated rats, neovascularization increased with the duration of the postcautery interval. The amount of corneal neovascularization was not significantly different in the irradiated and nonirradiated rats at any of the postcautery intervals studied. This investigation suggests that endothelial cell migration plays a more important role than cell replication in the pathogenesis of corneal angiogenesis in the Fischer 344 rat. Moreover, the suppression of corneal angiogenesis by irradiation may be dependent on the experimental conditions and species examined.

Intraocular tumors. A cytopathologic study.

The cytologic characteristics and histopathologic correlates of common ocular tumors were examined using (1) cytologic and histologic specimens prepared from enucleated eyes with retinoblastoma and melanoma, (2) cytologic specimens prepared from clinically obtained intraocular fluids from eyes with lymphoma, metastatic adenocarcinoma and retinoblastoma and (3) cytologic specimens prepared from orbital aspirates and cerebrospinal fluids from a patient in whom retinoblastoma had spread to the orbit and central nervous system. Retinoblastoma cells occurred singly and in clusters and were associated with abundant necrotic debris and portions of capillaries with perivascular tumor infiltrates. Melanoma cells frequently had prominent nucleoli and variable amounts of fine cytoplasmic pigmentation and were found individually and in groups. Lymphoma cells were noncohesive, with scant cytoplasm. Metastatic intraocular adenocarcinoma cells had well-defined borders, multiple nucleoli and vacuolated cytoplasm. In general, the cellular morphology in the cytologic and tissue preparations of the intraocular tumors correlated well with each other. The findings suggest that common primary and metastatic intraocular tumors can be differentiated in cytologic preparations.

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.

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 Masson's trichrome stain, and showed variably positive staining with Mallory's 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.

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.

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 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 greater than 63 days) could be induced by DSBT administration alone. In comparison, animals receiving autologous 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 specificities 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Associations between cyclosporine therapy and interstitial fibrosis in renal allograft biopsies.

A retrospective masked study of 120 consecutive renal transplant biopsies was performed to evaluate the potential associations of cyclosporine (CsA) therapy and other factors on the degree and progression of interstitial fibrosis (IF). Allograft biopsies were obtained from patients receiving CsA (CsA+; n = 59) and not receiving CsA (CsA-; n = 46); pretransplant donor biopsies were used as controls (n = 15). IF was evaluated by histologic grading (0-3+) as well as by quantitative morphometric measurements of Masson's trichrome stain positive material. Other biopsy measurements included the pattern of IF (focal, diffuse; graded 0-3+), and tubular epithelial cell reactivity, necrosis, and vacuolization (each graded 0-3+). Potential confounding variables were also considered, including time interval between transplant and biopsy; creatinine levels at the time of biopsy, 2 weeks and 10 weeks postbiopsy, and the last stable (baseline) creatinine prior to biopsy; recipient age, clinical evidence of rejection, and duration of rejection reactions; transplant number; and postbiopsy graft outcome. 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 transplant and biopsy was significantly (P less than 0.04) greater for the CsA- group, measures of creatinine and IF were normalized 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 less than 0.01) and the degree of IF as measured by morphometry (P less than 0.04) were significantly higher in the CsA+ group, but only for biopsies obtained greater than 6 months posttransplant. Evaluation of biopsies less than 6 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 significant increase in fibrosis relative to patients not receiving CsA.

Causes of death in renal transplant recipients. A review of autopsy findings from 1966 through 1985.

From 1966 through 1985, a total of 640 patients received 739 renal transplants at a single center transplantation program. Of 245 total deaths, a slide and chart review of all 116 autopsied cases (47%) identified the major causes of death as pneumonia (n = 43), sepsis (n = 32), hemorrhage (n = 15), peritonitis (n = 11), meningitis (n = 7), and pulmonary embolism (n = 5). Eighty-five (73.3%) of these patients died of complications directly associated with immunosuppression, almost all (n = 82) as a result of infection. Organisms most frequently identified at death were gram-negative bacilli (n = 72), Candida species (n = 23), cytomegalovirus (n = 17), enterococcus (n = 14), Staphylococcus aureus (n = 11), Aspergillus species (n = 10), Pneumocystis carinii (n = 5), and mycobacteria (n = 5). Significant associations were found between bolus steroid antirejection therapy and infection with Aspergillus cytomegalovirus. Diabetics had a higher incidence of fungal infections and bowel perforation than nondiabetics. During this 20-year period, overall one-year actual patient survival rates for the four respective five-year intervals increased dramatically (69.9%, 68.2%, 83.3%, and 91.8%), but the normalized death rate showed a smaller decrease for infectious vs noninfectious causes.