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A 64-year-old woman with mixed cellularity Hodgkin's disease diagnosed in 1972 developed a malignant lymphoma of the conjunctiva 14 years later. She had undergone combined chemotherapy and radiation therapy for Hodgkin's disease. Non-Hodgkin's lymphomas developing after Hodgkin's disease have been reported with increasing frequency in recent years. It is important to recognise a separate malignant lymphoma in a patient with Hodgkin's disease because of the different treatment offered for each of these diseases. [ABSTRACT FROM PUBLISHER]

We identified three eyes that had undergone enucleation after transscleral resection of uveal melanoma. Two enucleated eyes with microscopically positive margins of resection exhibited no evidence of residual melanoma and these patients were alive without metastasis with at least four years′ follow-up. One eye with a transected melanoma contained residual melanoma and that patient died with metastatic melanoma to the liver three years after enucleation. There appear to be at least two general types of positive surgical margins of resection of uveal melanoma: microscopically positive margins and macroscopically positive (transected) margins of resection.

MYCN-amplified RB1 wild-type (MYCN amp RB1 +/+ ) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCN amp RB1 +/+ from the most prevalent RB1 -/- retinoblastoma using pretreatment MRI and radiomics. Ninety-eight unilateral retinoblastoma patients (19 MYCN cases and 79 matched controls) were included. Tumors on T2-weighted MR images were manually delineated and validated by experienced radiologists. Radiomics analysis extracted 120 features per tumor. Several combinations of feature selection methods, oversampling techniques and machine learning (ML) classifiers were evaluated in a repeated fivefold cross-validation machine learning pipeline to yield the best-performing prediction model for MYCN. The best model used univariate feature selection, data oversampling (duplicating MYCN cases), and logistic regression classifier, achieving a mean AUC of 0.78 (SD 0.12). SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCN amp RB1 +/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCN amp RB1 +/+ and RB1 -/- retinoblastoma subtypes., (© 2024. The Author(s).)

Background MYCN -amplified RB1 wild-type ( MYCN A RB1 +/+ ) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCN A RB1 +/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCN A RB1 +/+ retinoblastoma and age-matched children with RB1 -/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing ( RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCN A RB1 +/+ retinoblastoma and 88 control children with RB1 -/- retinoblastoma. Children in the MYCN A RB1 +/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1 -/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCN A RB1 +/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCN A RB1 +/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCN A RB1 +/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.

Chronic Liver Diseases (CLD) are characterized by abnormal accumulation of collagen fibrils, neo-angiogenesis, and sinusoidal remodeling. Collagen deposition along with intrahepatic angiogenesis and sinusoidal remodeling alters sinusoid structure resulting in portal hypertension, liver failure, and other complications. Efforts were made to develop treatments for CLDs. However, the success of such treatments is limited and unpredictable. We report a strategy for CLD treatment by induction of integrin α v β 3 mediated cell apoptosis using a rationally designed protein (ProAgio). ProAgio is designed to target integrin α v β 3 at a novel site. Integrin α v β 3 is highly expressed in activated Hepatic Stellate Cells (HSC), angiogenic endothelium, and capillarized Liver Sinusoidal Endothelial Cells (LSEC). ProAgio induces apoptosis of these disease causative cells. Tests with liver fibrosis mouse models demonstrate that ProAgio reverses liver fibrosis and relieves blood flow resistance by depleting activated HSC and capillarized LSEC. Our studies demonstrate an effective approach for CLD treatment., (© 2021. The Author(s).)

The central vision-threatening event in glaucoma is dysfunction and loss of retinal ganglion cells (RGCs), thought to be promoted by local tissue deformations. Here, we sought to reduce tissue deformation near the optic nerve head by selectively stiffening the peripapillary sclera, i.e. the scleral region immediately adjacent to the optic nerve head. Previous scleral stiffening studies to treat glaucoma or myopia have used either pan-scleral stiffening (not regionally selective) or regionally selective stiffening with limited access to the posterior globe. We present a method for selectively stiffening the peripapillary sclera using a transpupillary annular light beam to activate methylene blue administered by retrobulbar injection. Unlike prior approaches to photocrosslinking in the eye, this approach avoids the damaging effects of ultraviolet light by employing red light. This targeted photocrosslinking approach successfully stiffened the peripapillary sclera at 6 weeks post-treatment, as measured by whole globe inflation testing. Specifically, strain was reduced by 47% when comparing treated vs. untreated sclera within the same eye (n = 7, p=0.0064) and by 54% when comparing the peripapillary sclera of treated vs. untreated eyes (n = 7, p<0.0001). Post-treatment characterization of RGCs (optic nerve axon counts/density, and grading), retinal function (electroretinography), and retinal histology revealed that photocrosslinking was associated with some ocular toxicity. We conclude that a transpupillary photocrosslinking approach enables selective scleral stiffening targeted to the peripapillary region that may be useful in future treatments of glaucoma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A 46-year-old patient with previously documented Ebola virus persistence in his ocular fluid, associated with severe panuveitis, developed a visually significant cataract. A multidisciplinary approach was taken to prevent and control infection. Ebola virus persistence was assessed before and during the operation to provide safe, vision-restorative phacoemulsification surgery.

Retinoblastoma (RB) is an ocular tumor of early childhood. Current treatments attempt to preserve visual function, but may spare chemoresistant tumor cells. One potential therapeutic target for RB is HER2, (ERBB2), expressed in RB in truncated form. In this study, we tested the hypothesis that Her2 DNA and RNA are expressed in RB tumors and adjacent retina. We examined 24 human RB tumors as well as normal-appearing adjacent retinal tissues for Her2 DNA and RNA expression by in situ hybridization. We also examined 28 RB tumors for HER2 protein immunoreactivity. 21/22 RB tumors expressed Her2 DNA and 14/19 tumors expressed Her2 RNA. In 17 paired cases, there were three cases in which Her2 DNA was detected, but not RNA. We also saw Her2 RNA signal in six instances of "normal" adjacent retinal tissue. Heterogeneous HER2 protein expression in specific tumor regions also was confirmed by quantitative HER2 immunohistochemistry. In summary, Her2 DNA and RNA are expressed in many RB tumors, and in some adjacent ocular tissues, with hetereogenous protein expression throughout. These results may provide important insights regarding RB tumor progression, and drug targeting approaches designed to spare the eye, preserve vision and improve quality of life for RB patients., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest., (Copyright: © 2019 Seigel et al.)

Purpose: Ciliary body mesectodermal leiomyoma is a rare, benign smooth muscle tumor that typically presents in women in the second to fourth decade of life. The diagnosis is typically based on clinical color, funduscopic appearance, transillumination properties, and B-scan ultrasonography., Methods: We present a patient with a 360° ciliary body mass with transillumination and ultrasonographic properties consistent with a ring melanoma., Results: This case emphasizes the difficulty in differentiating the benign leiomyoma from similar appearing malignant tumors such as melanoma., Conclusion: The eye was enucleated and the diagnosis was ring-shaped leiomyoma.

Purpose: To determine whether long-term cultured nondividing human retinal pigment epithelial (hRPE) cells are sensitive to oxidant-induced apoptosis and whether the Fas pathway is involved in the process., Methods: Confluent hRPE cells were maintained for 2 to 3 months in the basal medium (DMEM containing 2% fetal bovine serum) with one medium change per week. DNA synthesis was measured by incorporation of bromodeoxyuridine (BrdU) and the cell cycle was analyzed by flow cytometry. Intracellular glutathione (GSH) and glutathione disulfide (GSSG) were measured by HPLC. Apoptosis was triggered with the oxidant tert-butylhydroperoxide (tBH), recombinant soluble Fas ligand (sFasL), or agonistic anti-Fas antibody (CH-11). Cell viability was assessed by tetrazolium salt (WST-1) assay, and apoptosis was determined by measuring DNA cleavage or phosphatidylserine exposure. FasL and Fas proteins were detected by flow cytometry and Western blot. FasL and Fas transcripts were analyzed by RT-PCR., Results: After incubation in basal medium for more than 2 months, hRPE cells were largely nondividing and accumulated autofluorescent granules identified by electron microscopy to be lysosomes. Compared with proliferating hRPE cells, the nondividing cells had lower intracellular GSH, GSSG, and GSH/GSSG and a more oxidized redox potential (E(h)). Downregulation of Fas but upregulation of FasL was observed in these cells. The nondividing hRPE cells appeared more susceptible to tBH-induced apoptosis. Similar to proliferating hRPE cells, the apoptosis induced by tBH was preceded by induction of FasL, and antioxidants inhibited both FasL increase and apoptosis. Apoptosis was also inhibited with the antagonistic anti-Fas antibody ZB4. However, the nondividing hRPE cells had decreased sensitivity to apoptosis triggered by sFasL or CH-11., Conclusions: Long-term hRPE culture created cells that were nondividing and accumulated autofluorescent granules. The increased sensitivity to tBH-induced apoptosis in these cells was associated with intracellular oxidation and upregulation of FasL. These results suggest that an increase in FasL may contribute to the vulnerability of nondividing hRPE cells to oxidant-induced apoptosis.

Purpose: To characterize the pathologic features in retina, optic nerve, and extraocular muscle of mitochondrial superoxide dismutase (Sod2)-deficient mice, a model of increased mitochondrial production of reactive oxygen species., Methods: Morphometric and ultrastructural study of eyes of 43 homozygous sod2(tm1Cje-/-) mice and wild-type control animals. For retinal morphometric analysis, 32 manganese 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP)-treated animals aged either 9 to 10 days or 20 to 21 days were studied. Ultrastructural examination was performed on tissue from the treated animals, and 11 additional untreated mutant and control animals., Results: In treated Sod2-deficient animals, the photoreceptor layer was thinner centrally at 9 to 10 days than in control animals (mean 8.8 vs. 14.7 microm). By 20 to 21 days, all retinal layers apart from the outer nuclear layer and retinal pigment epithelium (RPE) were thinner centrally in mutant animals (total retinal thickness, 233.2 vs. 272.6 microm; combined nerve fiber layer, ganglion cell layer, and inner plexiform layer, 86.2 vs. 103.4 microm; inner nuclear layer, 51.8 vs. 60.3 microm; photoreceptors, 26.7 vs. 35.6 microm). Optic nerve cross-sectional area was less in 20- to 21-day-old treated Sod2-deficient animals than in control animals. Mitochondrial morphologic abnormalities (swelling, pale matrix, and disorganized cristae) were found predominantly in older mutant animals' (16 and 20 to 21 days) RPE and in extraocular muscle of a 16-day-old untreated mutant., Conclusions: In sod2(tm1Cje-/-) mice, there is relative progressive retinal thinning, with particular involvement of the inner retinal layers and an early effect on the photoreceptor layer, as well as mitochondrial morphologic abnormalities, all consistent with mitochondrial disease.

Purpose: To examine the histologic and ultrastructural changes in Bruch's membrane (BM) in apolipoprotein E deficient [ApoE(-)] mice in comparison with age-matched control animals., Methods: Two-month-old (group 1) and 8-month-old (group 2) normal control C57BL/6 mice and 2-month-old (group 3) and 8-month-old (group 4) ApoE(-) mice were studied. All groups of mice were fed a standard rodent diet. The mice were killed, serum lipid levels were determined, and the eyes were ultrastructurally examined using standard techniques to measure the thickness of BM. The area fraction of electron-lucent (EL) particles in BM was quantified using point-counting stereology., Results: The serum cholesterol levels of the ApoE(-) mice were significantly higher than those of the control mice (P = 0.0001). There was a significant thickening and EL particle accumulation in BM associated with age in the control animals. Group 2 had a thicker BM and more EL particle accumulation than group 1 (P = 0.0410 for thickness; P = 0.0042 for particle accumulation). Age-related changes were not seen in ApoE(-) mice; thickness and accumulation were similar in groups 3 and 4 (P = 0.50, thickness; P approximately/= 1.0, accumulation). Significant thickening and accumulation were seen in young ApoE(-) mice (group 3) versus young control animals (group 1; P = 0.008, thickening; P < 0.0001, EL particle accumulation). Group 4 ApoE(-) mice did not have a thicker BM or more EL particles than group 2 control animals (P = 0.2910, thickness; P = 0.35, EL particle accumulation). "Membrane-bounded" material (material between two membranes) was present significantly more frequently in ApoE(-) mice., Conclusions: ApoE(-) mice exhibit accumulation of EL particles at an earlier age and have more membrane-bounded material in BM than control mice. This material has ultrastructural similarities to basal linear deposit, which accumulates in age-related maculopathy.

Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as an oral anti-tussive agent and has shown very few toxic effects in animals or humans. Recently, we reported that noscapine binds stoichiometrically to tubulin and promotes microtubule polymerization. Noscapine causes growth arrest of tumor cells in mitosis and induces apoptosis of tumor cells in vitro. Previous experiments also showed that noscapine has potent antitumor activity in mice when administered parenterally or by gastric lavage. Here, we report that the anti-mitotic effect was specific to noscapine since closely related compounds did not inhibit the growth of a lymphoma cell line. In addition, noscapine was shown to be effective in reducing the growth of the lymphoma and increasing the survival of tumor-bearing mice when administered in the drinking water. It is noteworthy that, noscapine showed little or no toxicity to kidney, liver, heart, bone marrow, spleen or small intestine at tumor-suppressive doses. Furthermore, oral noscapine did not inhibit primary immune responses, which are critically dependent upon proliferation of lymphoid cells. Thus, our results indicate that noscapine has the potential to be an effective chemotherapeutic agent for the treatment of human cancer.

Purpose: The purpose of this study is to test the hypothesis that a subset of conjunctival melanocytic proliferations exists that cannot be reproducibly classified as benign, malignant, or indeterminate., Methods: Three groups of excisional biopsy specimens of conjunctival melanocytic proliferations were evaluated by 5 ophthalmic pathologists. These groups included lesions that were considered by the authors to represent benign (Group 1, n = 5), malignant (Group 2, n = 5) and indeterminate melanocytic proliferations (Group 3, n = 5). The panel classified the same sections in all 3 groups in a randomized, masked fashion, first without and then with a clinical history of patient age, sex and race. The kappa statistic (k) was used to quantify the degree of agreement among observers., Results: There was strong concordance among the panel for both Group 1 (benign, k = 0.76) and Group 2 (malignant, k = 0.70) melanocytic proliferations. There was no concordance of the panel for Group 3 (indeterminate) lesions (k = -0.045). The concordance for Groups 1 and 2 and lack of concordance for Group 3 lesions were independent of knowledge of clinical history of age, sex, and race., Conclusions: A subset of melanocytic proliferations of the conjunctiva exists that cannot be reproducibly classified by pathologists as benign, malignant, or indeterminate.

Purpose: The purpose of this study is to test the hypothesis that primary tumor vascularity in a murine model of intraocular melanoma positively correlates with the development and hematogenous spread of metastasis., Methods: Forty 12-week-old C57BL6 mice were inoculated in either the anterior chamber (AC) or posterior compartment (PC) of 1 eye with 5 x 10(5) cells/microL of Queens tissue culture melanoma cells. The inoculated eye was enucleated at 2 weeks; the mice were sacrificed at 4 weeks postinoculation, and necropsies were performed. The enucleated eyes were examined for histologic and ultrastructural features, including relationship of tumor cells to tumor vascular channels, vascular pattern, and mean vascular density., Results: Melanoma grew and was confined to the eye in 12 of 20 AC eyes and 10 of 20 PC eyes. Histologic and electron microscopic examination showed tumor invasion into vascular channels. Five of 12 AC tumors (42%) and 8 of 10 PC tumors (80%) metastasized. All of the AC tumors, but none of the PC tumors, that distantly metastasized also metastasized to ipsilateral cervical lymph nodes (P = .00535). There was no statistically significant difference of vascular pattern between the melanomas that did and did not metastasize to lungs in the PC group (P = .24), although there was a significant difference in the AC group (P = .02). Tumors with high-grade vascular patterns were more likely to metastasize than tumors with low-grade vascular patterns in the AC group. The mean vascular density positively correlated with the presence and number of metastases in both groups (P = .0000 and P < .001, respectively). There was no statistically significant difference of vascular pattern and mean vascular density for AC versus PC melanoma (P = .97)., Conclusions: The rate of metastasis in this murine intraocular melanoma model positively correlates with primary tumor vascularity. The melanoma metastasizes via invasion of tumor vascular channels. AC melanoma also metastasizes through regional lymphatics.

Purpose: To quantify morphologic changes in the choroid, including choriocapillaris and larger choroidal vessels, Bruch's membrane, and retinal pigment epithelium in eyes with age-related macular degeneration (AMD) and late ARM (age-related maculopathy)., Methods: The authors analyzed 40 eye bank eyes with late ARM (21 with the neovascular AMD and 19 with nonneovascular AMD) and compared them with 40 age-matched eyes without signs of late ARM (AMD). The eyes were processed for light microscopy, and seven variables were measured in the macular and peripheral regions with a digital filar micrometer., Results: There were no statistically significant differences observed between eyes with neovascular versus nonneovalcular AMD. The single most important difference between eyes with and without AMD was the amount of basal laminar deposit (P < 0.001). Eyes with AMD displayed fewer large choroidal vessels in the submacular choroid than eyes without AMD (3.5 +/- 1.5 mm-1 and 5.7 +/- 1.6 mm-1; P < 0.001). The submacular choriocapillaris density was higher in eyes with AMD (0.62 +/- 0.06) than in eyes without AMD (0.51 +/- 0.08; P < 0.001). The diameter of the large choroidal vessels in the peripheral choroid was increased in eyes with AMD (30 +/- 8 microns) compared to eyes without AMD (21.4 +/- 6.2 microns; P < 0.001). The peripheral choriocapillaris density displayed the same pattern as in the macular region in eyes with and without AMD., Conclusions: The amount of basal laminar deposit strongly correlates with the histologic presence of AMD. Eyes with AMD show differences of the density and diameter of choroidal blood vessels compared to eyes without AMD.

Background: We created a standardized model of severe Staphylococcus aureus endophthalmitis in the aphakic rabbit eye to test various treatment strategies involving corticosteroid administration in addition to vitrectomy and antibiotic treatment., Materials and Methods: In 71 aphakic New Zealand albino rabbit eyes, experimental endophthalmitis was created by injecting 10(5) colony-forming units of Staphylococcal aureus. The animals were divided into 5 groups. One control group was followed up without treatment, while 4 groups were treated with vitrectomy and intraocular cefazolin injection. Two groups were also treated with intramuscular methylprednisolone, 1 group beginning on the day of surgery and 1 group beginning on the following day. In the final group, dexamethasone, 400 micrograms, was injected into the vitreous cavity at the close of surgery. Culture results were compared on the first 2 days after surgery. Inflammatory scores, including development of total corneal opacity, were assessed over a 21-day follow-up period, and histopathologic grading was carried out at the conclusion of the clinical observations., Results: Simultaneous administration of systemic corticosteroids beginning on the day of vitrectomy decreased inflammatory scores 1 week after institution of therapy but did not affect final scores. Delay of initiation of intramuscular corticosteroid until the first postoperative day negated the positive effects. Administration of intraocular corticosteroids was associated with an increase in inflammatory scores throughout the period of observation, an increase in percentage of eyes that developed opaque corneas, an increase in choroidal inflammation graded moderate or severe, and an increase in retinal necrosis compared with vitrectomy and cefazolin injection alone., Conclusions: This data suggest caution in the use of intraocular corticosteroids in treatment of severe endophthalmitis.

Purpose: To compare the histologic, morphometric and nuclear DNA content of a group of benign and malignant melanocytic lesions of the iris., Methods: Forty-four surgically excised melanocytic lesions of the iris were histologically classified as nevus or melanoma. Morphometric analysis using a digital filar micrometer (LaSICO 1602N-10 and 5-4A) measured the mean size of the 10 largest nucleoli, and Feulgen staining and image cytometry (CAS 200 Cell Analysis Systems) analyzed the nuclear DNA ploidy in the lesions. Patient follow-up information was obtained whenever possible., Results: Sixteen cases were histologically classified as nevi and twenty-eight cases as melanoma. The mean of the 10 largest nucleoli of the nevi was smaller than the mean among the melanomas (1.772 microns [SD = 0.366] and 2.773 microns [SD = 0.565], respectively). Feulgen staining revealed that all lesions were diploid, with the exception of two hyperdiploid and two hypodiploid melanomas. Of the patients with follow-up information available, none with nevi developed a metastasis and two with melanoma died of metastatic disease., Conclusions: The histologic classification of iris melanocytic lesions (i.e., nevus versus melanoma) correlates to nucleolar size (P < 0.001) but not to nuclear DNA ploidy.

Purpose: To compare the effects of a lensectomy with and without intraocular lens (IOL) implantation on a neonatal rhesus monkey eye., Methods: A lensectomy and anterior vitrectomy was performed on 75 monkeys during the first 16 days of life; 21 of these monkeys also had an IOL implanted into the posterior chamber. The eyes were examined at regular intervals using biomicroscopy, applanation tonometry, and ophthalmoscopy., Results: The pseudophakic monkeys were studied until they were 92.5 +/- 5.8 weeks of age and the aphakic monkeys until they were 80.4 +/- 5.7 weeks of age. Pupillary membranes (100% versus 55.5%; P < 0.01) and lens regeneration into the pupillary aperture (28.6% versus 5.6%; P = 0.02) occurred more often in the pseudophakic than the aphakic eyes. As a result, the pseudophakic eyes required more reoperations than the aphakic eyes to keep the visual axis clear (P < 0.01). There was not a significant difference in the incidence of ocular hypertension between the pseudophakic and aphakic eyes (9.5% versus 12.7%; P = 0.34). Pupillary capture of the IOL optic occurred in 52% and haptic breakage in 33% of the pseudophakic eyes. All of the eyes with broken haptics had a prominent Soemmerring's ring varying in maximum thickness from 0.6 to 2 mm. Nine of the haptics from the seven eyes with broken IOLs had eroded into the iris, two into the ciliary body, and one into the anterior chamber., Conclusions: Implanting an IOL into a neonatal monkey eye after a lensectomy and anterior vitrectomy increases the likelihood of a reoperation being necessary. Haptics frequently erode into the iris and ciliary body and may break because of stress placed on the optic-haptic junction by forward movement of the IOL.

The immunocytologic characteristics of two formalin-fixed, paraffin-embedded corneas from patients with the iridocorneal endothelial (ICE) syndrome and unaffected control corneas were studied. Binding of polyclonal antisera to Factor VIII, S-100 protein, involucrin, neuron specific enolase (NSE), and the lectins peanut agglutinin and Ulex europaeus agglutinin-1 was performed using the standard peroxidase-anti-peroxidase method. We detected reactive patterns of monoclonal antibodies to cytokeratins (34BE12 is a 56-58 kD mouse IgG reactive to stratified epithelia; Pkk1 is a 44-54 kD mouse IgG reactive to simple epithelia; and KL1 is a 55-57 kD mouse IgG reactive to epidermis and simple epithelia) using the standard avidin-biotin complex method. Staining properties were similar for the polyclonal antisera, lectins, NSE, and chromogranin in corneas with ICE syndrome and in the controls. However, the cytokeratins 34BE12, Pkk1, and KL1 were detected in the endothelium of the corneas with the ICE syndrome but not in the controls. These findings suggest that various cytokeratins are expressed in the corneal endothelium in the ICE syndrome that are not expressed in unaffected corneal endothelium.

The peroxidase-antiperoxidase method was used to study ten surgically obtained human optic nerve gliomas (pilocytic astrocytomas). All tissues were formalin fixed and paraffin embedded. Primary antisera included glial fibrillary acidic protein (GFAP), HNK-1 (type 1 astrocyte precursor marker), A2B5 (type 2 astrocyte precursor marker), S-100, vimentin, myelin basic protein (MBP), laminin, keratin, cytokeratin, epithelial membrane antigen (EMA), and neuron-specific enolase (NSE). Neoplastic astrocytes in optic nerve gliomas stained with GFAP, HNK-1, S-100, and vimentin. Oligodendrocytes and myelin sheaths stained for MBP, and NSE stained surviving axons in the tumors. Neoplastic astrocytes did not stain for A2B5, keratin, cytokeratin, EMA, or laminin. These results suggest that human optic nerve gliomas (pilocytic astrocytomas) arise from type 1 astrocytes.

Complement is present in ocular fluids, but the molecular mechanism(s) restricting its activation to exogenous targets and not to autologous ocular cells are currently unknown. To clarify how this control is achieved, monoclonal antibody (mAb)-based techniques were used to examine the eye, the lacrimal gland, and ocular fluids for the decay-accelerating factor (DAF), a membrane regulatory protein which protects blood cells from autologous complement activation on their surfaces. Immunohistochemical staining of tissue sections revealed DAF antigen on corneal and conjunctival epithelia, corneal endothelium, trabecular meshwork, and retina, as well as on lacrimal gland acinar cells and in adjacent lumens. By flow cytometry, cultures of conjunctival epithelium exhibited the highest DAF levels and levels on corneal epithelium greater than corneal endothelium greater than conjunctival fibroblasts. Biosynthetic labeling of corneal endothelium yielded de novo DAF protein with an apparent molecular weight (Mr) of 75 kD, approximating that of blood cell DAF protein, and digestions of conjunctival epithelium with phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme which cleaves glycoinositolphospholipid membrane anchors, released approximately 70% of the ocular surface DAF protein similar to leukocyte surface DAF protein. Quantitations of DAF by radioimmunometric assay employing mAbs against two DAF epitopes revealed 325 ng/ml (n = 12), 4.8 ng/ml (n = 10), and 22.0 ng/ml (n = 8) of soluble DAF antigen in tears, aqueous humor, and vitreous humor, respectively. Western blot analyses of the tear DAF antigen revealed two DAF forms, one with an apparent Mr of 72 kD resembling membrane DAF forms in other sites, and a second with an apparent Mr of 100 kD, which is previously undescribed. Since DAF activity is essential physiologically in protecting blood cells from autologous complement attack, the identification of DAF on the ocular surface, intraocularly, in the lacrimal gland, and in tears suggests that DAF-mediated control of complement activation is also required in these locations.

Recent studies utilizing electron microscopy and immunohistochemistry have added to the understanding of the pathology of progressive supranuclear palsy. This article reviews the neuropathologic findings of progressive supranuclear palsy and includes two new case reports. Findings in the patients reported here include extensive neuronal loss with reactive gliosis in deep subcortical gray matter such as globus pallidus, subthalamic nuclei, substantia nigra, red nucleus, dentate nucleus, and inferior olives. Neurofibrillary tangles were also noted in thalamus, hypothalamus, striatum, nucleus basalis, locus ceruleus, basis pontis nuclei, midbrain, pontine, and medullary reticular formation as well as in various cranial nerve nuclei.