[show abstract][hide abstract] ABSTRACT: BACKGROUND: The purpose of this study is to report two cases of idiopathic uveitis with secondary epiretinal membrane (ERM) formation in order to describe histologic and immunohistochemical features that may help distinguish uveitic from idiopathic ERMs. METHODS: The study utilized a clinical case series and histopathological and immunohistochemical findings. RESULTS: There was no identifiable etiology of inflammation in either case. Histology and immunohistochemistry demonstrated a mixture of abundant inflammatory cells, including lymphocytes, histiocytes, plasma cells, and occasional eosinophils, among a stromal matrix composed of glial elements and condensed vitreous, but no retinal pigment epithelium (RPE) was present. The relative proportions of the various inflammatory cell types were assessed with immunohistochemistry, and among the lymphocyte population, T cells predominated over B cells. In one of the cases, there was an abundance of histiocytes, consistent with granulomatous uveitis, which was later confirmed on histology of the enucleated globe. CONCLUSIONS: Idiopathic ERM formation is thought to be secondary to glial cell migration that may require some involvement of RPE cells. The absence of RPE and abundance of inflammatory cells may be used to identify ERMs as secondary to uveitis.
Journal of ophthalmic inflammation and infection. 04/2012;
[show abstract][hide abstract] ABSTRACT: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk).
Prospective, multicenter study.
A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers.
Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status.
Patients were managed for their primary tumor and monitored for metastasis.
The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status.
The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.
[show abstract][hide abstract] ABSTRACT: To investigate the possible mutations in the carbohydrate sulfotransferase 6 (CHST6) gene of 2 unrelated cases of macular corneal dystrophy (MCD) and to report atypical stromal deposits in one of them.
Corneal tissues were stained with antisulfated keratan sulfate (KS), antitransforming growth factor beta 1-induced protein (TGFBIp), thioflavin-T, alcian blue, and Masson trichrome. Sequencing was performed to identify potential mutations in the CHST6 gene and the fourth and twelfth exons of the TGFBI gene.
Alcian blue staining revealed the presence of multiple subepithelial and intrastromal mucopolysaccharide deposits, confirming the diagnosis of MCD in both cases. Immunofluorescence staining in case 1 revealed the presence of sulfated KS only in the keratocytes and select endothelial cells, consistent with MCD type IA. Preferential expression of sulfated KS was observed in keratocytes and extracellular stromal matrix in case 2, consistent with MCD type II. Atypical subepithelial and superficial stromal deposits were observed in case 1, which stained positively with alcian blue, eosin, Masson trichrome, and thioflavin-T indicating the presence of hyaline and amyloid materials. CHST6 gene sequencing revealed 2 heterozygous mutations in case 1 (a p.Arg211Gln and a novel mutation of p.Arg177Gly) and a novel homozygous mutation of p.Pro186Arg in case 2. No mutations were found in exons 4 or 12 of the TGFBI gene in case 1.
Secondary hyalinosis and amyloidosis occur in a case of MCD type IA with a novel p.Arg177Gly mutation in CHST6. A novel p.Pro186Arg mutation in CHST6 is associated with MCD type II in an African American.
[show abstract][hide abstract] ABSTRACT: Both granular and lattice deposits are present in Avellino corneal dystrophy (ACD), primarily associated with the R124H mutation of transforming growth factor-β-induced (TGFBIp). We investigated the presence of these deposits in other TGFBI mutations and the use of Thioflavin-T (ThT), a fluorescent amyloid stain for characterizing corneal amyloid deposits.
Surgical corneal specimens of 3 unrelated patients clinically diagnosed with ACD were studied. Corneal sections from normal individuals and patients with prior lattice corneal dystrophy (LCD) were used as controls. Histochemical studies were performed with Congo red and Masson trichrome stains, and fluorescent imaging with scanning laser confocal microscopy was performed for ThT and anti-TGFBIp antibody staining.
Clinical and histopathological findings supported the diagnoses of ACD in these 3 cases in whom granular deposits stained with Masson trichrome and lattice deposits stained with ThT and Congo red showed birefringence and dichroism as expected. However, genotyping revealed a heterozygous R124C mutation in each case. In addition to classical stromal deposits, unique subepithelial TGFBIp aggregates, which stain with neither ThT nor trichrome, were observed. In control LCD sections, stromal deposits were stained with ThT but not with trichrome, confirming lack of granular deposits.
Our results demonstrate that both granular and lattice corneal deposits can be associated with R124C mutation in addition to the more common R124H mutation. An additional feature of nonhyaline, nonamyloid, TGFBIp subepithelial deposits might substantiate the categorization of such cases as a variant form of ACD. This study further validates ThT staining for detection of amyloid TGFBIp deposits.
[show abstract][hide abstract] ABSTRACT: To present a patient with a genotype usually associated with lattice corneal dystrophy but with clinical and histopathologic features of advanced Avellino corneal dystrophy.
Penetrating keratoplasty was performed with subsequent histopathologic analysis. For genetic testing, a 5-mL blood sample was taken after informed consent. Genetic sequencing was performed by the John and Marcia Carver Laboratory of the University of Iowa. The mutation was identified by direct sequencing through the positions of the coding sequences of the TGFBI gene that have been previously reported to have genetic variations (exons 4 and 11-14).
Corneal examination revealed bilateral lattice and multiple confluent subepithelial and anterior stromal granular opacities. Histopathologic examination showed amyloid deposits by Congo red stain and hyaline deposits by Masson trichrome stain, consistent with a diagnosis of Avellino dystrophy. Automated DNA sequencing revealed a heterozygous Arg124Cys (R124C) mutation in the coding sequence of the TGFBI gene on chromosome 5q31. Recurrent granular deposits developed in the corneal graft 14 months after surgery.
Our case presented with clinical and histopathologic findings consistent with a diagnosis of Avellino dystrophy and exhibited a genotype with R124C mutation. Avellino dystrophy has not previously been reported to be associated with the R124C mutation, which is usually associated with lattice corneal dystrophy. This also raises the issue as to whether classification of the corneal stromal dystrophies should be based primarily on phenotype/histopathology or on genotyping.
[show abstract][hide abstract] ABSTRACT: Imatinib mesylate (Gleevec((R))) is a well-established pharmacologic treatment for all phases of chronic myeloid leukemia and for advanced gastrointestinal stromal tumors (GISTs). Edema-related side effects are relatively common in imatinib therapy with the periocular skin representing one of the most common sites for localized edema. While the adverse effect of periorbital edema with imatinib is well documented in the oncology literature, there is limited reference to this common reaction in the ophthalmology literature. We report two patients with upper eyelid edema associated with imatinib therapy who required surgical intervention to ameliorate significant visual field obstruction. We highlight the details of each case including the histopathologic findings of excised redundant skin followed by a thorough review of the literature on imatinib related periorbital edema.
[show abstract][hide abstract] ABSTRACT: Purpose: To present the histologic and immunohistochemical findings of an epiretinal membrane overlying a combined hamartoma of the retina and retinal pigment epithelium.
Methods: An interventional case report.
Results: A 17-year-old healthy girl with a history of congenital cataract presented with a combined hamartoma of the retina and retinal pigment epithelium with prominent epiretinal membrane portion. Pars plana vitrectomy and membranectomy were performed, and the excised epiretinal membrane was submitted for routine histology and immunohistochemistry. Hematoxylin and eosin stain showed a monolayer of cells with an underlying basement membrane. Some of the nuclei were more epithelioid, consistent with retinal pigment epithelium (but without pigment in the cytoplasm), and other nuclei were more spindle-shaped, consistent with fibroglial elements. The initial immunostains suggested an admixture of retinal pigment epithelium and retinal elements.
Conclusion: To the authors' knowledge, this is the first study to use immunohistochemistry to elucidate the composition of these membranes. Future studies investigating the immunohistochemical profile of combined hamartomas are necessary.
[show abstract][hide abstract] ABSTRACT: To describe the histopathologic characteristics of a 51-year-old Castroviejo square graft that remained functional for more than 50 years and to describe the wound-healing characteristics over this period of time.
An 80-year-old woman with a history of keratoconus underwent penetrating keratoplasty with square grafts in 1956 and 1957 in the right and left eyes, respectively. The graft from the right eye was replaced in 2007, and the corneal specimen was submitted for histopathologic analysis.
Light microscopy demonstrated a smooth transition between host and donor stroma. Descemet's membrane was markedly thickened (>40 m) and laminated, and a very thin retrocorneal membrane was visible at high magnification.
This case provides an opportunity to observe the histopathology of corneal wound healing over a period of more than half a century.
[show abstract][hide abstract] ABSTRACT: To describe characteristic histopathologic markers in deep anterior lamellar keratoplasty (DALK) using pneumatic dissection: Anwar "big-bubble" technique.
Case reports. Deep stromal buttons from 2 patients with keratoconus who had undergone DALK surgery using the "big-bubble" technique were examined by light microscopy.
The histopathology of excised corneal buttons demonstrated multiple intrastromal spaces consistent with air bubbles. Apical stromal thinning seen clinically was not as readily appreciated on histopathology.
Pneumatic dissection in DALK produces diffuse intrastromal air bubbles that may mask the corneal thinning that usually characterizes keratoconus histopathologically. This is a characteristic finding of which ocular pathologists and corneal surgeons should be aware.
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to report a case of Clostridium perfringens keratitis, which led rapidly to panophthalmitis, with loss of the eye in a healthy patient.
Clinicopathologic case report, with a brief review of the literature. An otherwise healthy 50-year-old man without known risk factors developed a corneal ulcer, and within 48 hours, he lost all vision, with corneal perforation and panophthalmitis. The eye was enucleated, and the globe was examined histopathologically.
The cornea was sampled for Gram staining and cultures, which revealed gram-positive rods and the growth of C. perfringens in the anaerobic culture. The globe revealed corneal necrosis and perforation, with acute inflammation in all layers of the eye. Gram-positive bacilli, consistent with C. perfringens, were identified in the vitreous cavity abscess.
C. perfringens endophthalmitis cases from penetrating injuries are fulminant infections, with near universal loss of the eye, whereas C. perfringens keratitis cases are relatively indolent infections. To the best of our knowledge, this is the first report of a C. perfringens keratitis, which led rapidly to panophthalmitis. This aggressive behavior of C. perfringens has not been described previously in human subjects.
[show abstract][hide abstract] ABSTRACT: To report a case of secondary corneal amyloidosis in a chronic hydrops lesion of a patient with pellucid marginal degeneration (PMD).
Clinicopathologic case report with a review of the literature. A 63-year-old man with PMD developed acute hydrops in 1999, which never resolved and became an elevated, gelatinous lesion with peripheral neovascularization. Penetrating keratoplasty was performed in 2005, and the excised button was examined histopathologically.
The excised button revealed substantial subepithelial acellular deposits consistent with amyloid in the area of the unresolved gelatinous lesion, overlying a disruption in Descemet membrane, confirming the diagnosis of secondary corneal amyloidosis.
Secondary corneal amyloidosis is a corneal response to chronic injury and irritation that is not commonly reported and often overlooked. To the best of our knowledge, this is the first report of a dramatic secondary amyloidosis deposit in the chronic hydrops lesion of a patient with PMD.