Failure of radiation therapy in orbital xanthogranuloma.

PURPOSE: The efficacy of radiation therapy in orbital xanthogranuloma in patients who fail medical therapy is unclear. The purpose of this study was to ascertain its effectiveness. METHODS: The records of 11 cases were reviewed retrospectively for histopathologic findings, age, gender, site of involvement, clinical manifestations, and outcomes of treatment. The case histories of the 4 patients treated with radiation, all of whom had failed medical treatment, were described. RESULTS: Of 11 patients, 5 were female, and all were white. The age range at the time of presentation was 25 to 85 years. Nine patients had bilateral involvement. Five patients, all of whom had bilateral disease, had systemic manifestations or autoimmune disease thought to be related to their orbital disease. In general, patients treated with systemic corticosteroids had at least a partial response of their lesion. However, none of the 4 patients treated with orbital radiation (3 of whom had not responded to steroid treatment and 1 of whom had responded only to high-dose steroids) experienced improvement, and at least 3 experienced exacerbation of their disease. The histologic features before treatment in all cases were similar and consistent with xanthogranuloma. CONCLUSION: Orbital xanthogranuloma may be a unilateral or bilateral condition. Particularly when bilateral, it may be associated with similar lesions elsewhere or with systemic autoimmune disorders. The results of this study suggest that fractionated radiotherapy not only may be ineffective but also may exacerbate the progression of the orbital lesions in patients who do not respond to medical therapy or who are steroid dependent on intolerable doses of medication.

Calcareous degeneration of host-donor interface after descemet membrane stripping with automated endothelial keratoplasty.

PURPOSE: To report a case of host-donor interface calcification after Descemet membrane stripping with automated endothelial keratoplasty (DSAEK). METHODS: Review of the patient's clinical records and histopathologic examination of the donor corneal lamella from repeat DSAEK performed subsequent to the original DSAEK. RESULTS: Review of the clinical record of the patient revealed an ocular history of Fuchs dystrophy and pseudophakic bullous keratoplasty that was treated with DSAEK. She later developed corneal edema and a partially detached donor lamella and underwent repeat DSAEK. Histopathologic and transmission electron microscopic evaluations of the corneal lamella revealed calcium deposits in the host-donor interface. CONCLUSIONS: Calcareous degeneration of the host-donor interface after DSAEK is reported as a novel postoperative complication of DSAEK. Calcium deposits in the host-donor interface after DSAEK should be considered in the differential diagnosis of interface opacity after this procedure, particularly in patients with predisposing systemic or local risk factors such as retained phosphate-containing viscoelastic material, excessive postoperative inflammation, or use of phosphate-buffered, postoperative topical medications.

Epibulbar foreign body granuloma masquerading as extrascleral extension following brachytherapy for choroidal melanoma.

PURPOSE: To describe a patient with epibulbar foreign body granuloma following brachytherapy for choroidal melanoma and to illustrate the echographic features that aided in the differential diagnosis. METHODS: Observational case report. Patient had multiple clinical exams over time to evaluate a treated choroidal melanoma. PATIENTS: A 61-year-old man presented for echographic follow-up examination following treatment for choroidal melanoma. An epibulbar lesion was noted adjacent to the site of the previously treated choroidal melanoma. Incisional biopsy and histologic evaluation were required. RESULTS: Ultrasonography revealed regression of the intraocular tumor; however, an oval epibulbar mass with irregular internal structure, irregular reflectivity, and no vascularity was noted. The echographic features were not typical of extrascleral extension of choroidal melanoma. Histopathologic evaluation showed fibrous connective tissue with an intense infiltrate of histiocytes with occasional giant cells and rare birefringent foreign body materials. CONCLUSION: Foreign body granuloma should be considered in the echographic differential diagnosis of an atypical extrascleral lesion following uveal melanoma brachytherapy.

Acanthamoeba sclerokeratitis.

BACKGROUND: Acanthamoeba scleritis is an uncommon but severe complication of acanthamoeba keratitis. We report the clinical and histopathologic features of a patient with acanthamoeba sclerokeratitis. METHODS: Review of the patient's clinical records and histopathologic examination of the globe including light microscopy and transmission electron microscopy. RESULTS: Review of the clinical record of the patient revealed a past ocular history of penetrating keratoplasty for persistent acanthamoeba keratitis. Later in the course of treatment, the patient developed nodular necrotizing scleritis with culture-proven viable acanthamoeba in this area. She underwent enucleation of the eye for persistent acanthamoeba sclerokeratitis. Histopathologic examination of the globe revealed no acanthamoeba cysts or trophozoites at the site of crotherapy. CONCLUSION: Our study provides evidence for the invasion of acanthamoeba organisms into the sclera in a case of acanthamoeba keratitis. The presence of trophozites in scleral tissue may exacerbate the immune response leading to nodular scleritis.

A study of histopathological features of latanoprost-treated irides with or without darkening compared with non-latanoprost-treated irides.

OBJECTIVES: To study the histopathological features of latanoprost-treated irides with or without darkening, compared with non-latanoprost-treated irides. METHODS: Iridectomy specimens and patient history forms were independently examined by 3 ophthalmic pathologists in a masked fashion. Specimens were evaluated for premalignant changes and for differences in level of pigmentation and degrees of cellularity, inflammation, and vascular abnormalities. RESULTS: The specimens consisted of 22 latanoprost-treated darkened irides, 35 latanoprost-treated irides without darkening, and 35 non-latanoprost-treated irides. There was a statistically significant decrease in the number of nuclear invaginations and prominent nucleoli in latanoprost-treated darkened irides compared with the other 2 groups (P = .004 and P = .005, respectively). The average thickness and pigmentation of the anterior border layer was greater in the latanoprost-treated darkened irides than in the other 2 groups (P = .03 and P = .02, respectively). The latanoprost-treated darkened irides had increased pigmentation of the stroma (P < .001), stromal fibroblasts (P < .001), melanocytes (P = .005), vascular endothelium (P = .02), and adventitia (P < .001) relative to the other 2 groups. CONCLUSIONS: There is no histopathological evidence of premalignant changes in latanoprost-treated darkened irides. The latanoprost-induced iris color changes are due to a thickening of the anterior border layer and an increased amount of melanin in the anterior border layer and within the stromal melanocytes.

Safety of intravitreal ketorolac and diclofenac: an electroretinographic and histopathologic study.

OBJECTIVE: To determine the clinical, histologic, and electroretinographic effects in the rabbit retina of escalating doses of two intravitreally delivered nonsteroidal anti-inflammatory drugs (NSAIDs): ketorolac and diclofenac. METHODS: Right eyes received a single 0.1 mL injection of either ketorolac (500-6000 microg/0.1 mL) or diclofenac (300-1500 microg/0.1 mL) prepared in balanced salt solution (BSS). Left eyes served as controls and received BSS. Dark- and light-adapted electroretinograms (ERG) were obtained at baseline and 4 and 8 weeks postinjection. Enucleated eyes were examined histologically. RESULTS: Ophthalmic examinations demonstrated no signs of intraocular inflammation or retinal toxicity. Intraocular pressure measurements remained similar between NSAID injected and control eyes. Histologic and ERG studies of eyes injected with 6000 microg ketorolac and >or=500 microg diclofenac demonstrated toxicity. In contrast, doses up to 3000 microg ketorolac demonstrated enhanced b-wave amplitude responses. Delayed drug toxicity was observed for the highest doses of both NSAIDs. CONCLUSIONS: Intravitreal 3000 microg ketorolac and 300 microg diclofenac were nontoxic in this animal study, and may offer an effective and safer alternative to intravitreal corticosteroids.

Histopathologic characteristics of choroidal melanoma in eyes enucleated after iodine 125 brachytherapy in the collaborative ocular melanoma study.

OBJECTIVE: To describe the histopathologic findings in eyes with uveal melanoma that had secondary enucleation after failed brachytherapy plaque treatment. METHODS: Histopathologic findings in eyes that had secondary enucleation after plaque radiation therapy in the Collaborative Ocular Melanoma Study (COMS) were reported on a standardized data form. The findings were compared with eyes that had primary enucleation for uveal melanoma. RESULTS: Seventy-five eyes that had secondary enucleation were studied. Compared with primary enucleations, tumors in the irradiated eyes had lower mitotic activity, a smaller proportion of histologically intact tumor, more inflammation, more fibrosis, and more vascular damage within the tumor. In addition, compared with primary enucleations, eyes previously irradiated had a higher frequency of retinal invasion by the tumor and greater damage to the retinal vasculature, consistent with radiation retinopathy; neovascularization of the iris; and vitreous hemorrhage. Tumor growth or extrascleral extension was confirmed histopathologically in 25 of 42 eyes (60%) enucleated because of a reported failure of local control. CONCLUSIONS: Eyes with secondary enucleation after brachytherapy differ histopathologically from eyes with primary enucleation for uveal melanoma. These histopathologic differences may be due to the effects of radiation, tissue conditions related to plaque failure, and, in some cases, tumor growth. In 40% of eyes enucleated because of suspected failure of local control, increased tumor size could not be histologically confirmed.

Electron microscopic investigation of the lens capsule and conjunctival tissues in individuals with clinically unilateral pseudoexfoliation syndrome.

PURPOSE: To determine the presence of pseudoexfoliative material in the unaffected eyes of patients with clinically unilateral pseudoexfoliation syndrome. DESIGN: Prospective observational case series. PARTICIPANTS: Thirty-two consecutive patients with clinically unilateral pseudoexfoliation syndrome, undergoing routine cataract surgery. METHODS: Transmission electron microscopy (TEM) was used to examine conjunctival and anterior lens capsule specimens in affected and unaffected eyes. MAIN OUTCOME MEASURE: Presence of characteristic pseudoexfoliation syndrome findings on TEM. RESULTS: Transmission electron microscopy demonstrated pseudoexfoliative material on either the anterior capsule or conjunctival sample from the clinically unaffected eye in 26 of the 32 patients with clinically unilateral pseudoexfoliation syndrome (81%; 95% confidence interval, 64%-93%). CONCLUSION: The results suggest that the seemingly uninvolved eye in a patient with clinically unilateral pseudoexfoliation syndrome has an 81% likelihood of being affected ultrastructurally. Several population studies examining conversion rates from unilateral to bilateral disease have found a similar proportion of patients with bilateral pseudoexfoliation syndrome in the later decades of life.

Histopathologic and trypsin digestion studies of the retina in incontinentia pigmenti.

OBJECTIVE: To report the ocular histopathologic features of a 55-year-old patient with incontinentia pigmenti retinopathy. DESIGN: Observational case report. PARTICIPANT: A 55-year-old patient with incontinentia pigmenti retinopathy. METHODS: Examination of eyes by light microscopy and retinal trypsin digestion. MAIN OUTCOME MEASURES: Clinical and histopathological findings. RESULTS: Histopathologic examination disclosed inner retinal ischemic atrophy, capillary beading, arteriolar-venous anastomoses, preretinal neovascularization, vasculopathy located at the junction of central vascular and peripheral avascular retina, retinal tears, and tractional retinoschisis. CONCLUSIONS: Patients with retinal manifestations of incontinentia pigmenti may progress to proliferative vitreoretinopathy or retinal detachment and should be observed closely over the course of their lifetime.

Ocular clusterin expression in von Hippel-Lindau disease.

PURPOSE: Clusterin is a multifunctional glycoprotein. Its mRNA is ubiquitously expressed, with high levels in von Hippel-Lindau (VHL) target organs such as the brain, liver, kidney, and adrenal medulla. Decreased clusterin secretion has been reported in renal cell carcinoma associated with VHL disease. The purpose of this study was to investigate ocular clusterin expression in VHL disease. METHODS: This retrospective case series included nine eyes with retinal hemangioblastoma/hemangioma associated with VHL disease, one eye from a patient with a history of VHL disease and central nervous system hemangioblastomas but without ocular lesions, one surgically-excised optic nerve with optic nerve hemangioblastoma/hemangioma, and three normal control eyes. Ocular specimens were evaluated by routine histology, immunohistochemistry for clusterin expression, and molecular detection of clusterin transcripts within ocular VHL hemangioblastomas compared with normal tissue from the same eye using microdissection and quantitative real-time PCR. RESULTS: All retinal hemangioblastoma were composed of typical VHL tumor cells admixed with small vascular channels as well as glial cells. Marked decrease of clusterin immunoreactivity was detected in all retinal hemangioblastoma and the optic nerve hemangioblastoma, whereas positive clusterin reactivity of the vascular and glial components was similar to that of normal retina. Quantitative real-time PCR analysis confirmed the decrease of clusterin mRNA in the VHL associated retinal hemangioblastoma and optic nerve hemangioblastoma in five cases. CONCLUSIONS: Clusterin shows possible important functions in tumor suppression by the VHL gene product (pVHL) and the potential to be a novel biomarker in retinal hemangioblastoma associated VHL disease. Further investigation of clusterin may provide better understanding of retinal hemangioblastoma associated with VHL disease.

Iron toxicity as a potential factor in AMD.

While it has been known for years that iron overload is associated with retinal degeneration in the context of ocular siderosis, intraocular hemorrhage, and the hereditary diseases aceruloplasminemia and pantothenate kinase associated neurodegeneration, recent evidence suggests that age-related macular degeneration (AMD) may also be exacerbated by retinal iron overload. In the retina, iron is necessary for normal cellular function. Iron overload, however, can cause retinal toxicity through the generation of oxygen free radicals. Histopathology of eyes with macular degeneration has shown elevated levels of iron in the retinal pigment epithelium, Bruch membrane, and within drusen, some of which was chelatable in vitro with deferoxamine. In this review, the authors summarize the evidence that iron overload may contribute to AMD pathogenesis. It is hoped that continued investigation of the role of iron and iron associated proteins in the retina will uncover clues to AMD pathogenesis and lead to new preventative or therapeutic options.

Histopathologic and immunologic aspects of alphacor artificial corneal failure.

PURPOSE: To describe the histopathologic and immunologic characteristics of late artificial corneal failure in a small series of patients who underwent AlphaCor implantation and to elucidate the mechanisms involved. DESIGN: Clinicopathologic case series. METHODS: Three patients were diagnosed with corneal melting during the late postoperative period and required the removal of the devices. The explanted devices embedded within the corneal tissues were examined by light microscopy, electron microscopy, and immunohistochemical studies. RESULTS: Light microscopic examination of the specimens disclosed adequate biointegration with no foreign body response. Immunofluorescence studies of the skirt exhibited expression of inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), and some interferon gamma (IFN-gamma). The keratocytes stained positively for Thy-1 and smooth muscle actin but negatively for CD34. CONCLUSIONS: Although these findings confirm the occurrence of biointegration, myofibroblastic differentiation of the ingrowing keratocytes is a prominent feature.

Floretlike cells in in situ and prolapsed orbital fat.

PURPOSE: Orbital pleomorphic lipoma has been rarely reported in the literature. Although floretlike cells are characteristic of pleomorphic lipoma, they are not pathognomonic. We reviewed cases of prolapsed orbital fat and exenteration specimens to determine the significance of presence of these cells in the diagnosis of orbital pleomorphic lipoma. DESIGN: Retrospective interventional case series with clinicopathologic correlation. PARTICIPANTS: Seventy-two specimens of 45 patients with prolapsed orbital fat and 74 exenteration specimens as controls. INTERVENTION: Histologic review of the specimens including light microscopy, Masson trichrome staining, immunostaining for S100, CD34, CD68, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and transmission electron microscopy and review of clinical records and analysis of the data with generalized estimation equation. MAIN OUTCOME MEASURE: Evidence of histologic abnormalities in histologic specimens and clinical and demographic data. RESULTS: Floretlike cells were present in 31 of 72 (43%) specimens of prolapsed orbital fat and in 12 of 74 (16%) orbital exenterations. Fewer than 6 florets were present in twenty 40x high-power fields in 15 (48%), 6 to 10 in 9 (29%), and >10 in 7 (23%) specimens. The florets stained positive for CD34 but not for S100 or CD68. TUNEL assay revealed significant nuclear pyknosis, and transmission electron microscopy disclosed spindle-shaped cells with abundant rough endoplasmic reticulum and no basement membrane. The mean age of patients with prolapsed orbital fat with florets was 67 years (range, 52-86). Of 31 samples, 29 (94%) were from males. Of 30 samples, 29 (97%) were located in the superotemporal conjunctiva; only one was located in the lower lid. There was significant association between the presence of florets and location of the prolapsed orbital fat (P = 0.0013) and gender (P = 0.0015). CONCLUSION: Floretlike cells may be present in in situ and prolapsed orbital fat as a degenerative process. What some have called "orbital pleomorphic lipoma" is in fact only age-related orbital fat prolapse.

Non-contiguous recurrence or secondary choroidal melanoma following plaque radiotherapy.

Non-contiguous local recurrence of posterior uveal melanoma occurs rarely after plaque therapy. A 50-year-old white first presented with choroidal melanoma. He underwent therapy with episcleral iodine-125 radioactive plaque therapy. Nine years later fundus evaluation revealed a new pigmented lesion in the inferotemporal equatorial area. Patient was considered to have a non-contiguous recurrent melanoma and the eye was enucleated. Histologic microscopic examination disclosed a 3 x 1.8 mm densely pigmented tumour internal to the choroid at the equator. The tumour was composed of large round cells with round nuclei, prominent nucleoli, abundant cytoplasm and spindle-shaped cells with spindle-shaped nuclei and prominent nucleoli. The tumour extended through the retina. The superior nasal area of plaque therapy had extensive chorioretinal atrophy with loss of retinal pigment epithelium, thinning of the retina and thinning and depigmentation of the choroids. Within this area of atrophy, there was a pigmented lesion composed by densely packed, spindle-shaped cells with spindle-shaped nuclei. Our patient illustrated non-contiguous recurrence of choroidal melanoma, such finding raises concerns about physiopathology and treatment of choroidal melanoma.

Ocular autopsy and histopathologic features of child abuse.

PURPOSE: To study the ocular histopathologic features in eyes of children with fatal suspected child abuse. DESIGN: Retrospective case series. PARTICIPANTS: One hundred eighteen autopsy cases of known or suspected child abuse. METHODS: The ocular autopsy and histopathologic features of a cohort of consecutive cases of known or presumed child abuse submitted by Maryland's Office of the Chief Medical Examiner or Johns Hopkins Hospital to the Wilmer Eye Pathology Laboratory were tabulated. MAIN OUTCOME MEASURE: Ocular hemorrhage or structural abnormality. RESULTS: Retinal hemorrhage was present in 44% of cases. Circumferential folds with macular schisis cavities were present in 23% of cases and were bilateral in half of those cases. Peripapillary scleral hemorrhage was present in 38% of cases, and subdural hemorrhage was present in the distal optic nerve in 46% of cases. Hemosiderin was present in 27% of cases. CONCLUSIONS: Intraretinal hemorrhages, circumferential macular folds with schisis cavities, peripapillary scleral hemorrhages, and subdural hemorrhages are common pathologic findings in cases of fatal known or suspected child abuse. Their presence on autopsy should raise the suspicion of shaking or blunt nonaccidental trauma.

Asymptomatic conjunctival mucosa-associated lymphoid tissue-type lymphoma with presumed intraocular involvement.

PURPOSE: To report a case of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma with presumed intraocular involvement. METHODS: Observational case report. RESULTS: A 73-year-old white man presented for a routine eye examination and was found to have a salmon-colored bulbar conjunctival mass of the left eye. Ultrasound showed a low-reflective mass with diffuse thickening of the ciliary body and choroid. Immunohistochemistry and flow cytometry of an incisional biopsy specimen suggested a polyclonal lesion. Treatment with topical steroids yielded no clinical improvement, and excisional biopsy was performed. A diagnosis of MALT lymphoma was made after polymerase chain reaction (PCR) analysis of the immunoglobulin heavy chain (IgH) locus revealed a clonal B-cell population. CONCLUSIONS: Conjunctival MALT lymphoma can present without symptoms and can extend intraocularly. PCR analysis of the IgH locus can identify lesion clonality when immunohistochemistry and flow cytometry fail to do so.

Advanced glycation end products and receptors in Fuchs' dystrophy corneas undergoing Descemet's stripping with endothelial keratoplasty.

PURPOSE: To describe the histopathologic features of Descemet's membrane (DM) obtained from Fuchs' endothelial corneal dystrophy (FECD) corneas undergoing Descemet's stripping with endothelial keratoplasty (DSEK) and to assess the presence of advanced glycation end products (AGEs) and their receptors in FECD endothelium and DM. DESIGN: Prospective observational case series. PARTICIPANTS: Five eyes of 5 patients undergoing DSEK for FECD and 4 normal control eyebank corneas. METHODS: Descemet's membrane and corneal endothelium from FECD patients undergoing DSEK were assessed with hematoxylin-eosin staining and immunohistochemistry for AGEs, receptor of AGEs (RAGE), and galectin 3 (AGE-R3). MAIN OUTCOME MEASURES: Histopathologic abnormalities and presence of AGEs, RAGE, and AGE-R3 in DSEK specimens. RESULTS: Histopathologic assessment of DSEK specimens from FECD patients disclosed thickening and nodularity of DM and loss of endothelial cells. Immunohistochemical staining of FECD DM for AGE, RAGE, and AGE-R3 showed an abundance of AGEs in the anterior portion of DM, mild positivity for RAGE, and moderate positivity for AGE-R3. CONCLUSIONS: Tissue quality after DSEK is sufficient to allow detailed histopathologic analysis. The presence of AGEs, RAGE, and AGE-R3 in DM and corneal endothelium of FECD patients supports a link between accumulation of AGEs, oxidative stress, and corneal endothelial cell apoptosis in the pathogenesis of FECD.