June 2012

Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases.

PURPOSE: To describe the incidence of associated infection, respiratory compromise, apparent intranasal cyst, as well as sex, laterality, and age at presentation in 64 infants with dacryocystocele and to assess characteristics associated with successful interventions. METHODS: A retrospective chart review of all patients with dacryocystocele seen at Children's Hospital Boston between 1996 and 2010 was performed. Inclusion criteria were accuracy of diagnosis, treatment, and follow-up at our institution. Interventions were divided into 3 categories: procedures that did not require general anesthesia; simple procedures requiring general anesthesia, such as nasolacrimal probing with or without stent or balloon dilation; and more complex procedures under general anesthesia, specifically, those aided by intranasal endoscopy. RESULTS: Of the 90 identified patients, 64 met inclusion criteria. The majority of patients were female (63%) and had unilateral involvement (77%). More than one-half of all patients were successfully treated without anesthesia; however, patients presenting with infection were more likely to be treated with a simple procedure under general anesthesia. All patients treated endoscopically had intranasal cysts. Age, sex, and infection did not predict the use of intranasal endoscopy. Bilaterality of dacryocystocele was associated with the use of an endoscopic approach. CONCLUSIONS: Many infants with dacryocystocoele can be successfully treated without general anesthesia. The incidence of occult intranasal cyst among those treated without endoscopy remains unknown. Patients who were treated under general anesthesia but without the use of nasal endoscopy were more likely to have an infected system, but the clinical significance of this association is not clear.

PURPOSE: Bone marrow-derived mesenchymal stem cells (MSCs) hold great promise for wound healing and tissue regeneration. In the present study, we investigated the impact of corneal injury on the homeostasis of endogenous MSCs, and the potential of MSCs to home to injured tissue and promote corneal repair. METHODS: Corneal injury in mice was induced by thermal cauterization. Circulating MSCs were quantified by flow cytometric analysis. Ex vivo expanded red Q-dot-labeled or GFP+ bone marrow-derived MSCs were intravenously injected after injury and detected using epifluorescence microscopy. Corneal fluorescein staining was performed to evaluate epithelial regeneration. RESULTS: Following the induction of corneal injury in mice, a 2-fold increase in the frequency of circulating endogenous MSCs was observed within 48 hours of injury, which was accompanied by increased levels of the stem cell chemoattractants, substance P and SDF-1, in both the injured cornea and blood. Systemically administered MSCs homed to the injured cornea, but not to the normal cornea, and showed long-term survival. In addition, in the setting of corneal injury, MSC administration showed significant and rapid corneal epithelial regeneration. CONCLUSIONS: These findings provide novel evidence that corneal injury causes significant mobilization of endogenous MSCs into blood, and that MSCs home specifically to the injured cornea and promote regeneration, highlighting the therapeutic implications of MSC-mediated tissue repair in corneal injury.

BACKGROUND: Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard-field color stereoscopic retinal photography (ETDRS photos) has been a gold standard for determining diabetic retinopathy (DR) severity. The Automated Retinal Imaging System (ARIS™, model 110, Visual Pathways, Inc., Prescott, AZ) acquires seven-sequential color stereoscopic digital images (ARIS images) by a semiautomated technician-run process generally corresponding to ETDRS photos. We assessed the correlation between a single semiautomated ARIS imaging session without any re-imaging and ETDRS photos performed by a certified photographer for the determination of DR severity. METHODS: Two independent masked readers graded mydriatic ARIS images and ETDRS photos. A third masked retinal specialist adjudicated discrepancies. Correlation between the two modalities was compared using weighted-κ statistics. RESULTS: We evaluated 211 eyes of 106 patients with varying levels of DR. Partially ungradable images were present in 3.4% of ETDRS photos versus 31.8% of ARIS images. Exact agreement and agreement within one level between ETDRS photos and ARIS images using only completely gradable image sets occurred in 69% (κ=0.81) and 90% of cases, respectively. Exact agreement for clinically significant macular edema was 92.1% (κ=0.59). There was 100% agreement for eyes with high-risk proliferative DR. Within one level of DR severity, 100% agreement occurred for the following: questionable nonproliferative DR (NPDR), moderate NPDR, and severe NPDR. CONCLUSIONS: Results suggest that semiautomated ARIS images compare favorably with ETDRS photos when full image sets can be obtained; however, partially ungradable image sets occurred almost 10 times more frequently with ARIS images than with ETDRS photos. In the two-thirds of cases where ARIS images can be utilized, ARIS can obtain retinal images comparable to ETDRS photos while requiring less highly trained personnel than generally needed for standard ETDRS photos.

The antiepileptic drug vigabatrin is known to cause retinal and visual dysfunction, particularly visual field defects, in some patients. Electroretinography (ERG) is used in an attempt to identify adverse effects of vigabatrin (VGB) in patients who are not candidates for conventional perimetry. We report data from 114 pediatric patients taking VGB referred for clinical evaluation; median age at test was 22.9 (2.4 to 266.1) months, and median duration of VGB use was 9.7 (0.3 to 140.7) months. Twenty-seven of them were tested longitudinally (3 to 12 ERG tests). ERG responses to full-field stimuli were recorded in scotopic and photopic conditions, and results were compared to responses from healthy control subjects. We found that abnormalities of photoreceptor and post-receptor ERG responses are frequent in these young patients. The most frequently abnormal scotopic parameter was post-receptor sensitivity, log σ, derived from the b-wave stimulus-response function; the most frequently abnormal photopic parameter was the implicit time of the OFF response (d-wave) to a long (150 ms) flash. Abnormal 30-Hz flicker response amplitude, previously reported to be a predictor of visual field loss, occurred infrequently. For the group as a whole, none of the ERG parameters changed significantly with increasing duration of VGB use. Four of the 27 patients tested longitudinally showed systematic worsening of log σ with duration of VGB use. In a subset of patients who underwent perimetry (N = 39), there was no significant association of any ERG parameter with visual field defects. We cannot determine whether the ERG abnormalities we found were due solely to the effects of VGB. We caution against over-reliance on the ERG to monitor pediatric patients for VGB toxicity and recommend further development of a reliable test of peripheral vision to supplant ERG testing.

PURPOSE: To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU). METHODS: C57BL/6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-γ, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-Ab) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured. RESULTS: AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression. CONCLUSIONS: AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR.

PURPOSE: The purpose of this study was to report the levels of tissue plasminogen activator in liquefied suprachoroidal hemorrhage. METHODS: An interventional case report of a 61-year-old woman who underwent drainage sclerotomy for choroidal hemorrhage. RESULTS: A 61-year-old pseudophakic woman underwent pars plana vitrectomy and fluid-gas exchange for retinal detachment in her right eye and developed postoperative serous choroidal detachments with large hemorrhages. Drainage sclerotomy was performed 18 days after the initial development of suprachoroidal hemorrhage. Sample of the liquefied hemorrhage and serum sample collected during sclerotomy were tested for tissue plasminogen activator levels using the antibody tissue plasminogen activator-enzyme immunoassay test. Hemorrhage tissue plasminogen activator levels were three times the levels present in the serum. CONCLUSION: Tissue plasminogen activator may be involved in the process of suprachoroidal hemorrhage liquefaction.