Spontaneous resolution of a postvitrectomy macular hole retinal detachment.

PURPOSE: The purpose of this report was to describe a case of spontaneous resolution of a large postvitrectomy macular hole retinal detachment. METHODS: Case report and optical coherence tomography imaging. RESULTS: A 64-year-old man with history of macula-off retinal detachment and 4 previous vitrectomies in the left eye developed a macular hole and associated retinal detachment 3 months after his last vitreoretinal surgery. Two months later, examination revealed that the macular hole had spontaneously closed, and the retinal detachment had resolved. CONCLUSION: Spontaneous resolution of macular hole-associated retinal detachment in a previously vitrectomized eye has not been reported previously. Changes in tangential traction by the associated epiretinal membrane, improvement of the cystoid changes noted at the edge of the macular hole, and/or proliferation of glial tissue to bridge the hole, along with the absorption of the subretinal fluid by the retinal pigment epithelium pump contributed to this rare event have been hyphothesized.

Ultra-wide-field fluorescein angiography in retinal disease.

PURPOSE OF REVIEW: Ultra-wide-field fluorescein angiography (UWFA), which captures up to 200° of retina in a single image, now affords us the ability to angiographically examine the parts of the retina previously not photographable. Here, we review the role of UWFA in the management of retinal disease. RECENT FINDINGS: UWFA effectively images the abnormality in a variety of retinal conditions, including diabetic retinopathy, retinal vein occlusion, sickle cell retinopathy, uveitis, and pediatric retinal disease, in turn guiding both diagnosis and management of these conditions. SUMMARY: UWFA is a useful imaging modality that is expected to become increasingly incorporated into the practice of retina. This will likely fuel the studies to determine how to reconcile the findings from UWFA with practice guidelines based on the studies conducted prior to the development of UWFA.

Re-evaluating our perspective on retinal artery occlusion from carotid dissection: a report of three cases and review of the literature.

BACKGROUND AND OBJECTIVE: Retinal artery occlusion from carotid dissection is rare and classically considered a post-traumatic phenomenon occurring in young patients and associated with additional symptoms of dissection such as neck pain, headache, or focal neurological deficits. PATIENTS AND METHODS: The authors report three cases of retinal artery occlusion due to carotid artery dissection and briefly review the literature. RESULTS: Antecedent trauma or neck injury was reported in only 42% (five of 12) of previously reported cases and in none of the three cases presented here. All three patients in this series initially denied symptoms such as headache or neck pain; however, one patient's wife later recalled her husband experiencing minor neck soreness several days prior to visual loss. In 17% (two of 12) of previously reported cases, no additional symptoms of carotid dissection were reported. CONCLUSION: These cases highlight the importance of considering carotid dissection in young patients with retinal artery occlusion, even in the absence of a report of recent trauma or associated symptoms such as pain.

Paraneoplastic dermatomyositis related to a chondrosarcoma involving the cavernous sinus.

Approximately one third of all cases of dermatomyositis may be associated with malignancy. We describe a patient with unexplained rash, joint pain, and muscle weakness, who subsequently developed a cavernous sinus syndrome due to a central nervous system chondrosarcoma. Discovery of this tumor and further dermatologic evaluation, including skin biopsy, resulted in diagnosis of paraneoplastic dermatomyositis due to cavernous sinus chondrosarcoma.

Fundus autofluorescence in ampiginous choroiditis.

Fundus autofluorescence (FAF) is being increasingly employed in the evaluation of retinal diseases. We report the first description of FAF findings during the natural history of ampiginous choroiditis and correlate these findings to fundus photography, infrared imaging, and cross-sectional optical coherence tomography. In a patient with a 12-month recurring, relapsing course of ampiginous choroiditis, there was a predictable pattern of FAF findings. At the time of presentation with a whitish-yellow, creamy clinical lesion, FAF reveals a diffuse, subtle hyperautofluorescence at the site of activity. As the clinical lesion fades, the FAF takes on a more intense, discrete, coalesced hyperautofluorescence, which decreases and becomes stippled over time, eventually giving way to a patch of hypoautofluorescence at the site of inactivity. Examination over the patient's long course suggests that FAF evolves predictably during exacerbations and remissions, and the FAF findings reveal activity well after the clinical lesion resolves. FAF is a simple, noninvasive, and effective modality for following the evolution of ampiginous choroiditis.

Gaze-evoked amaurosis from orbital breast carcinoma metastasis.

Gaze-evoked amaurosis (GEA) is a transient monocular vision loss provoked by eccentric gaze. Gaze-evoked amaurosis has been associated with a variety of orbital lesions, most commonly optic nerve sheath meningiomas and cavernous hemangiomas. The authors describe the first report in the literature of GEA as the presenting symptom of an orbital metastasis. The patient was a 47-year-old woman with a history of breast cancer with no known history of metastasis or active disease who presented with several weeks of vision loss in the OD upon rightward gaze. She was found to have enophthalmos and optic disc edema of the OD. Imaging revealed an intraorbital lesion, and a biopsy was consistent with a scirrhous metastasis of her breast carcinoma. This case highlights the importance of considering orbital metastases among the differential for gaze-evoked amaurosis.

Intraorbital metastasis from solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare spindle cell tumor of mesenchymal origin that usually arises from pleura or pericardium but can also arise from many extraserosal sites. Although more than 50 cases of primary SFT of the orbit have been reported, there are no reports to date of a malignant nonophthalmic SFT metastasizing in the orbital soft tissues (although sphenoid wing bony involvement has been reported). The authors report here the first case of a patient with intraorbital metastasis of a CD34-positive malignant SFT. The patient was a 57-year-old man with a history of malignant pleural SFT and a prior kidney metastasis. He presented with the rapid appearance of proptosis and massive conjunctival chemosis preventing eyelid closure, and he was found to have a well-circumscribed metastasis to his lateral rectus muscle. Surgical excision cured his ocular symptoms, although he died 3 months later from brain and widespread metastases.

ERG monitoring of retinal function during systemic chemotherapy for retinoblastoma.

BACKGROUND/AIMS: We have previously introduced electroretinography (ERG) as a proxy for visual function to monitor for retinal toxicity due to intra-arterial chemotherapy for retinoblastoma in young children. In this paper, we report ERG results for patients with retinoblastoma receiving initial treatment with systemic chemotherapy. METHODS: Inclusion criteria were patients presenting with retinoblastoma at <3 months of age or <6.0 kg in weight, with large tumours not amenable to local laser treatment, cryotherapy or plaque brachytherapy. Patients received intravenous carboplatin 18.7 mg/kg every 3-5 weeks, contingent on recovery of blood counts, until they had grown sufficiently to receive intra-arterial chemotherapy. ERG was performed during examination under anaesthesia at monthly intervals, using contact lens electrodes and a hand-held ganzfeld stimulator. 30-Hertz flicker responses are reported. RESULTS: Four patients were treated for bilateral retinoblastoma. All eyes responded well to systemic chemotherapy. 30-Hertz flicker ERGs improved during treatment in all eyes, significantly in six of eight eyes, and at least in one eye of each patient. CONCLUSION: Effective systemic chemotherapy for retinoblastoma in children who are too small for intra-arterial chemotherapy is compatible with significant increases in ERG amplitudes, even in eyes presenting with extinguished ERGs. ERG signals may increase independent of resolution of retinal detachment.

Characterization of computed tomography scan abnormalities in patients with biopsy-proven hepatic metastases from uveal melanoma.

OBJECTIVES: To describe the computed tomography (CT) features in patients with biopsy-proven hepatic metastases of uveal melanoma and correlate these findings with survival. METHODS: The medical records of patients with uveal melanoma evaluated at Memorial Sloan-Kettering Cancer Center from January 1998 to September 2009 were reviewed. Inclusion criteria were biopsy-proven liver metastasis and CT scan images available within 2 months of biopsy. Exclusion criteria were prior systemic or liver-directed therapy for uveal melanoma. Statistical analyses were carried out using the t test, χ(2) test, and Kaplan-Meier log-rank analyses. RESULTS: Of 505 medical records reviewed, 76 were selected for study. Characteristic CT findings included multiple (68 patients [90%]), hypodense (100%), heterogeneous (100%), and enhancing (100%) hepatic lesions with a mean dominant lesion size of 46.8 cm(2). Eighteen patients (24%) exhibited hepatomegaly. Predominant lesion size larger than 100 cm(2), hepatomegaly, and ascites correlated with a lower survival rate (P = .008, P < .001, and P < .001, respectively). Radiographic evidence of extrahepatic metastases was present in 40 patients (53%). However, the presence of extrahepatic metastases did not affect survival. The results of at least 1 liver function test were abnormal in 46 of 67 patients (69%), and elevation of at least 1 serum transaminase and elevation of alkaline phosphatase were associated with larger lesions (P = .009 and P = .004, respectively) and hepatomegaly (P < .001 for both). CONCLUSIONS: Radiographic evidence of predominant lesion size larger than 100 cm(2), hepatomegaly, and ascites-but not radiographic evidence of extrahepatic metastases-correlate with a lower survival rate in patients with biopsy-proven hepatic metastases of uveal melanoma.

Macrophage polarization in the maculae of age-related macular degeneration: a pilot study.

Macrophages can be polarized to exhibit either pro-inflammatory M1 or pro-angiogenic M2 phenotypes, but have high phenotypic plasticity. This pilot study investigated macrophage polarization in the macular retina and choroid of age-related macular degeneration (AMD) and non-AMD subjects, as well as in AMD choroidal neovascular membranes (CNVM). All specimens were evaluated for routine histopathology. Quantitative real-time polymerase chain reaction for representative M1 (CXCL11) and M2 (CCL22) transcripts were performed on macular choroidal trephines (MCT) of 19 AMD and nine non-AMD eye bank eyes, on the microdissected macular retinal cells from the archived slides of five geographic atrophic AMD, five exudative/neovascular AMD, and eight normal autopsied eyes, and on microdissected inflammatory cells from two surgically removed CNVM that did not respond to anti-vascular endothelial growth factor (VEGF) therapy. High M2-chemokine transcript and a low ratio of M1 to M2 chemokine transcript were found in aging non-AMD MCT. Advanced AMD maculae had a higher M1 to M2 chemokine transcript ratio compared to normal autopsied eyes. Macrophages in the two CNVM of patients unresponsive to anti-VEGF therapy were polarized toward either M1 or M2 phenotypes. The number of M2 macrophages was increased compared to M1 macrophages in normal aging eyes. A pathological shift of macrophage polarization may play a potential role in AMD pathogenesis.

Therapeutic implications of the emerging molecular biology of uveal melanoma.

Uveal melanoma represents the most common primary intraocular malignancy in adults. Although uveal and cutaneous melanomas both arise from melanocytes, uveal melanoma is clinically and biologically distinct from its more common cutaneous counterpart. Metastasis occurs frequently in this disease, and once distant spread occurs, outcomes are poor. No effective systemic therapies are currently available; however, recent advances in our understanding of the biology of this rare and devastating disease, combined with the growing availability of targeted agents, which can be used to rationally exploit these findings, hold the promise for novel and effective therapies in the foreseeable future. Herein, we review our rapidly growing understanding of the molecular biology of uveal melanoma, including the pathogenic roles of GNAQ (guanine nucleotide binding protein q polypeptide)/11, PTEN (phosphatase and tensin homolog), IGF (insulin-like growth factor)/IGF-1 receptor, MET (hepatocyte growth factor), BAP1 [breast cancer 1, early onset (BRCA1)-associated protein-1], and other key molecules, potential therapeutic strategies derived from this emerging biology, and the next generation of recently initiated clinical trials for the treatment of advanced uveal melanoma.

Intra-arterial and oral digoxin therapy for retinoblastoma.

PURPOSE: Preclinical studies demonstrate that cardiac glycosides such as ouabain and digoxin have antitumor effects on retinoblastoma cells in vitro and in a xenograft murine model of retinoblastoma. METHODS: Based on these findings, we report a case of intra-arterial followed by systemic oral digoxin therapy in a patient with unilateral retinoblastoma that had failed prior intra-arterial chemotherapy. RESULTS: Oral administration of digoxin produced no effect, while intra-arterial digoxin therapy produced a modest but measurable response that was likely limited by the inability to achieve sustained drug concentration in the eye. CONCLUSIONS: This case highlights both the potential promise and limitations of cardiac glycoside therapy in retinoblastoma.

Primary melanoma of the optic nerve in a patient with 16-year follow up.

Primary melanoma of the optic nerve is rare. Limited reports in the literature have been the subject of considerable controversy, as many of these melanomas have later been found to be metastatic disease or local extensions of a juxtapapillary choroidal melanoma. Moreover, these have often been reported in patients with a history of ocular or oculocutaneous pigmentary disorders. The authors present a case of primary melanoma of the optic nerve in a patient with no history of pigmentary disorder and 16 years of follow up.

Descemet's stripping automated endothelial keratoplasty in a patient with four glaucoma tubes.

Descemet's stripping automated endothelial keratoplasty (DSAEK) is an increasingly popular techniquefor transplanting corneal endothelial cells. The presence of glaucoma, and especially glaucoma tubes, however, renders the DSAEK procedure more challenging. Here, we present a case of DSAEK in a patient with quadruple glaucoma tubes.

Ophthalmic pathology of Nance-Horan syndrome: case report and review of the literature.

BACKGROUND: Nance-Horan syndrome (NHS) is a rare X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies due in most cases to a mutation in the NHS gene. MATERIAL AND METHODS: We present a case of clinical manifestation and ocular pathology in a patient with NHS. This article also reviews and discusses the relevant literature. RESULTS: Classic and novel ocular pathological findings of a young male with NHS are described, including congenital cataracts, infantile glaucoma, scleral staphyloma, and severe retinal cystoid degeneration. CONCLUSIONS: We report a new pathological finding of severe retinal cystoid degeneration in this NHS patient and confirm abnormal development of the anterior chamber angle structure. These findings, coupled with our analysis of the available NHS literature, provide new understanding of the histopathological basis of ocular abnormalities and vision loss in NHS.

Enhanced HtrA2/Omi expression in oxidative injury to retinal pigment epithelial cells and murine models of neurodegeneration.

PURPOSE: To investigate the role of HtrA2/Omi, a nuclear-encoded mitochondrial serine protease with a proapoptosis function, under H(2)O(2)-induced oxidative stress in human RPE, in the Ccl2(-)(/)(-)Cx3cr1(-)(/)(-) double-knockout (DKO) mouse retina, and the HtrA2/Omi-deficient mice. METHODS: Oxidative stress was induced in ARPE-19 cells by 1 mM H(2)O(2) for 2 hours. HtrA2/Omi and caspase-3 expression was evaluated using RQ-PCR, immunohistochemistry, or Western blot. Cell viability was detected by MTT assay. HtrA2/Omi expression in the subcellular components and activated caspase-3 were measured. These processes were also evaluated in cells treated with UCF-101, an HtrA2/Omi inhibitor or in cells subjected to RNAi against HtrA2/Omi. Oxidative stress was assayed and compared in retinas of DKO and wild-type (WT) mice by determining serum NADPH oxidase subunits and nitrite levels. Transmission electron microscopy was used to view the retinal ultrastructure of the HtrA2/Omi-deficient mice. RESULTS: H(2)O(2)-induced oxidative damage resulted in HtrA2/Omi translocation from mitochondria to cytosol, leading to RPE cell apoptosis via a caspase-mediated pathway. Treatment of RPE cells with UCF-101 reduced the cytosolic translocation of HtrA2/Omi, attenuated caspase-3 activation, and decreased apoptosis. After specific HtrA2 downregulation, increased cell viability was measured in H(2)O(2)-treated ARPE-19 cells. Retina of DKO mice exhibit increased oxidative stress and upregulation of HtrA2/Omi. Fewer and abnormal mitochondria were found in HtrA2/Omi(-)(/)(-) photoreceptors and RPE. CONCLUSIONS: These findings suggest that HtrA2/Omi is related to RPE apoptosis due to oxidative stress, which may play an important role in the integrity of mitochondria and the pathogenesis of AMD.

Limbal stem cell deficiency arising from systemic chemotherapy with hydroxycarbamide.

PURPOSE: The purpose of this study was to report a case of limbal stem cell deficiency (LSCD) after systemic chemotherapy with hydroxycarbamide. METHODS: Clinical manifestations and pathology are detailed. RESULTS: We describe the case of a woman with sickle cell disease, who developed bilateral LSCD after treatment with hydroxycarbamide. Histologic examination confirmed the diagnosis of LSCD, revealing goblet cells, inflammatory cells, deposits of new collagen components, and neovascularization in the peripheral cornea. Matrix metalloproteinase-3, fibronectin, and collagen III were also detected in the lesions. CONCLUSIONS: The systemic use of the antineoplastic drug, hydroxycarbamide, may cause severe LSCD. We recommend that a medication history, including that of cytotoxic drugs, be considered in evaluating LSCD.

Molecular pathology of age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch's membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress.