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Patel M, Vavvas DG. Spontaneous resolution of a postvitrectomy macular hole retinal detachment. Retin Cases Brief Rep 2014;8(3):161-3.Abstract

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.

Isayama T, Chen Y, Kono M, Fabre E, Slavsky M, DeGrip WJ, Ma J-X, Crouch RK, Makino CL. Coexpression of three opsins in cone photoreceptors of the salamander Ambystoma tigrinum. J Comp Neurol 2014;522(10):2249-65.Abstract
Although more than one type of visual opsin is present in the retina of most vertebrates, it was thought that each type of photoreceptor expresses only one opsin. However, evidence has accumulated that some photoreceptors contain more than one opsin, in many cases as a result of a developmental transition from the expression of one opsin to another. The salamander UV-sensitive (UV) cone is particularly notable because it contains three opsins (Makino and Dodd [1996] J Gen Physiol 108:27-34). Two opsin types are expressed at levels more than 100 times lower than the level of the primary opsin. Here, immunohistochemical experiments identified the primary component as a UV cone opsin and the two minor components as the short wavelength-sensitive (S) and long wavelength-sensitive (L) cone opsins. Based on single-cell recordings of 156 photoreceptors, the presence of three components in UV cones of hatchlings and terrestrial adults ruled out a developmental transition. There was no evidence for multiple opsin types within rods or S cones, but immunohistochemistry and partial bleaching in conjunction with single-cell recording revealed that both single and double L cones contained low levels of short wavelength-sensitive pigments in addition to the main L visual pigment. These results raise the possibility that coexpression of multiple opsins in other vertebrates was overlooked because a minor component absorbing at short wavelengths was masked by the main visual pigment or because the expression level of a component absorbing at long wavelengths was exceedingly low.
Bleier BS, Healy DY, Chhabra N, Freitag S. Compartmental endoscopic surgical anatomy of the medial intraconal orbital space. Int Forum Allergy Rhinol 2014;4(7):587-91.Abstract

BACKGROUND: Surgical management of intraconal pathology represents the next frontier in endoscopic endonasal surgery. Despite this, the medial intraconal space remains a relatively unexplored region, secondary to its variable and technically demanding anatomy. The purpose of this study is to define the neurovascular structures in this region and introduce a compartmentalized approach to enhance surgical planning. METHODS: This study was an institutional review board (IRB)-exempt endoscopic anatomic study in 10 cadaveric orbits. After dissection of the medial intraconal space, the pattern and trajectory of the oculomotor nerve and ophthalmic arterial arborizations were analyzed. The position of all vessels as well as the length of the oculomotor trunk and branches relative to the sphenoid face were calculated. RESULTS: A mean of 1.5 arterial branches were identified (n = 15; range, 1-4) at a mean of 8.8 mm from the sphenoid face (range, 4-15 mm). The majority of the arteries (n = 7) inserted adjacent to the midline of medial rectus. The oculomotor nerve inserted at the level of the sphenoid face and arborized with a large proximal trunk 5.5 ± 1.1 mm in length and multiple branches extending 13.2 ± 2.7 mm from the sphenoid face. The most anterior nerve and vascular pedicle were identified at 17.0 and 15.0 mm from the sphenoid face, respectively. CONCLUSION: The neurovascular supply to the medial rectus muscle describes a varied but predictable pattern. This data allows the compartmentalization of the medial intraconal space into 3 zones relative to the neurovascular supply. These zones inform the complexity of the dissection and provide a guideline for safe medial rectus retraction relative to the fixed landmark of the sphenoid face.

Lin YB, Gardiner MF. Fingernail-induced corneal abrasions: case series from an ophthalmology emergency department. Cornea 2014;33(7):691-5.Abstract
PURPOSE: Fingernail-induced corneal abrasions are one of the most common eye injuries that present to the emergency department, and yet there is little literature available to offer guidelines for management. We analyzed the treatment used in cases of fingernail-induced corneal abrasions that presented to the Massachusetts Eye and Ear Infirmary Emergency Department and studied its relationship to the development of complications such as recurrent erosion syndrome and infection. METHODS: We performed a retrospective review of 99 patients who presented to the Massachusetts Eye and Ear Infirmary Emergency Department with fingernail-induced corneal abrasions between January 1, 2009 and December 31, 2009. We followed the patients for 12 months and documented demographics, nature of the injury, treatment, and complications. RESULTS: The average age was 29.4 (range, 2-89) years. Forty-four percent (n = 44) were female and 56% (n = 55) were male. Of the 99 subjects, 39 had a full 12 month follow-up, and 7 developed a complication from the injury. Compared with the 32 subjects without complications, there was no difference in age or gender. However, there was a significant difference in that adults scratched by another adult were more highly represented in the group with complications (43%, n = 3/7 vs. 3%, n = 1/32; P = 0.0017). There was no significant difference in outcome by treatment used. CONCLUSIONS: This is the largest fingernail-induced corneal abrasion study completed to date. Patients are at risk of developing complications, but there is scant evidenced-based literature available for treating this common injury. Prospective trials should be performed to better optimize and standardize treatments.
Turalba AV, Pasquale LR. Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide. Clin Ophthalmol 2014;8:1311-6.Abstract
OBJECTIVE: To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. DESIGN: Retrospective comparative case series. PARTICIPANTS: Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. METHODS: A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. MAIN OUTCOME MEASURES: Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. RESULTS: Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. CONCLUSIONS: Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery.
Liu C, Chen Y, Kochevar IE, Jurkunas UV. Decreased DJ-1 leads to impaired Nrf2-regulated antioxidant defense and increased UV-A-induced apoptosis in corneal endothelial cells. Invest Ophthalmol Vis Sci 2014;55(9):5551-60.Abstract
PURPOSE: To investigate the role of DJ-1 in Nrf2-regulated antioxidant defense in corneal endothelial cells (CECs) at baseline and in response to ultraviolet A (UV-A)-induced oxidative stress. METHODS: DJ-1-deficient CECs were obtained by transfection of an immortalized normal human corneal endothelial cell line (HCECi) with DJ-1 small interfering RNA (siRNA) or by isolation of CECs from ex vivo corneas of DJ-1 knockout mice. Levels of reactive oxygen species (ROS), protein carbonyls, Nrf2 subcellular localization, Nrf2 target genes, and protein interaction between Keap1/Nrf2 and Cul3/Nrf2 were compared between normal and DJ-1-deficient CECs. Oxidative stress was induced by irradiating HCECi cells with UV-A, and cell death and levels of activated caspase3 and phospho-p53 were determined. RESULTS: DJ-1 siRNA-treated cells exhibited increased levels of ROS production and protein carbonyls as well as a 2.2-fold decrease in nuclear Nrf2 protein when compared to controls. DJ-1 downregulation led to attenuated gene expression of Nrf2 and its target genes HO-1 and NQO1. Similar levels of Nrf2 inhibitor, Keap1, and Cul3/Nrf2 and Keap1/Nrf2 were observed in DJ-1 siRNA-treated cells as compared to controls. Ultraviolet A irradiation resulted in a 3.0-fold increase in cell death and elevated levels of activated caspase3 and phospho-p53 in DJ-1 siRNA-treated cells compared to controls. CONCLUSIONS: Downregulation of DJ-1 impairs nuclear translocation of Nrf2, causing decreased antioxidant gene expression and increased oxidative damage. The decline in DJ-1 levels leads to heightened CEC susceptibility to UV-A light by activating p53-dependent apoptosis. Targeting the DJ-1-Nrf2 axis may provide a potential therapeutic approach for enhancing antioxidant defense in corneal endothelial disorders.
Yadav P, Jakobiec FA, De Castro DK, Mendoza PR, Fay A. Extruded, partially disintegrated, poly-HEMA orbital implant (AlphaSphere). Ophthalmic Plast Reconstr Surg 2014;30(4):e86-91.Abstract
A 54-year-old diabetic man underwent enucleation for endophthalmitis. Secondary implantation of a 2-hydroxyethyl methacrylate (HEMA) sphere (AlphaSphere, Addition Technology) was performed 2 weeks later. Six weeks after insertion, noninfectious disintegration of sutured tissue planes represented by Tenon's capsule, rectus muscle, and conjunctiva occurred, requiring removal of the fragmenting implant before uncontrolled extrusion occurred. Histopathologic analysis revealed an absence of infectious pathogens and no tissue necrosis, but rather breakup of the implant material that elicited a granulomatous response with sparse T-lymphocytes and almost no polymorphonuclear leukocytes. This distinctively designed poly-HEMA orbital implant incited a dramatic and irreversible host tissue response. Investigation of other cases will be necessary to determine the frequency of such a complication and should include rigorous histopathologic techniques.
Sweigard HJ, Yanai R, Gaissert P, Saint-Geniez M, Kataoka K, Thanos A, Stahl GL, Lambris JD, Connor KM. The alternative complement pathway regulates pathological angiogenesis in the retina. FASEB J 2014;28(7):3171-82.Abstract
A defining feature in proliferative retinopathies is the formation of pathological neovessels. In these diseases, the balance between neovessel formation and regression determines blindness, making the modulation of neovessel growth highly desirable. The role of the immune system in these retinopathies is of increasing interest, but it is not completely understood. We investigated the role of the alternative complement pathway during the formation and resolution of aberrant neovascularization. We used alternative complement pathway-deficient (Fb(-/-)) mice and age- and strain-matched control mice to assess neovessel development and regression in an oxygen-induced retinopathy (OIR) mouse model. In the control mice, we found increased transcription of Fb after OIR treatment. In the Fb(-/-) mice, we prepared retinal flatmounts and identified an increased number of neovessels, peaking at postnatal day 17 (P17; P=0.001). Subjecting human umbilical vein endothelial cells (HUVECs) to low oxygen, mimicking a characteristic of neovessels, decreased the expression of the complement inhibitor Cd55. Finally, using laser capture microdissection (LCM) to isolate the neovessels after OIR, we found decreased expression of Cd55 (P=0.005). Together, our data implicate the alternative complement pathway in facilitating neovessel clearance by down-regulating the complement inhibitor Cd55 specifically on neovessels, allowing for their targeted removal while leaving the established vasculature intact.-Sweigard, J. H., Yanai, R., Gaissert, P., Saint-Geniez, M., Kataoka, K., Thanos, A., Stahl, G. L., Lambris, J. D., Connor, K. M. The alternative complement pathway regulates pathological angiogenesis in the retina.
Karamichos D, Hutcheon AEK, Zieske JD. Reversal of fibrosis by TGF-β3 in a 3D in vitro model. Exp Eye Res 2014;124:31-6.Abstract
Corneal scarring following moderate to severe injury is inevitable. Despite significant advancements in the field, current treatments following these types of injuries are limited, and often, the visual recovery is poor. One of the problems and limitations is that corneal wound healing is a complex process, involving corneal cells, extracellular matrix components and growth factors. Therefore, further understanding is required, along with new treatments and techniques to reduce or prevent corneal scarring following injury. Two isoforms of transforming growth factor-beta (TGF-β), TGF-β1 and -β3 (T1 and T3, respectively), are associated with corneal wound healing. T1 has been shown to drive the corneal keratocytes to differentiate into myofibroblasts; whereas, T3 has been found to inhibit fibrotic markers. In the current study, we examined whether the fibrotic characteristics expressed by human corneal fibroblasts (HCF) in our 3-dimensional (3D) construct following T1 stimulation could be reversed by introducing T3 to the in vitro system. To do this, HCF were isolated and cultured in 10% serum, and when they reached confluence, the cells were stimulated with a stable Vitamin C (VitC) derivative for 4 weeks, which allowed them to secrete a self-assembled matrix. Three conditions were tested: (1) CONTROL: 10% serum (S) only, (2) T1: 10%S + T1, or (3) Rescue: 10%S + T1 for two weeks and then switched to 10%S + T3 for another two weeks. At the end of 4 weeks, the constructs were processed for analysis by indirect-immunofluorescence (IF) and transmission electron microscopy (TEM). Different collagens that are normally present in healthy corneas in vivo, such as Type I and V, as well as Type III, which is a fibrotic indicator, were examined. In addition, we examined smooth muscle actin (SMA), a marker of myofibroblasts, and thrombospondin-1 (TSP-1), a multifunctional matrix protein known to activate the latent complex of TGF-β and appear upon wounding in vivo. Our data showed high expression of collagens type I and V under all conditions throughout the 3D constructs; however, type III and SMA expression were higher in the constructs that were stimulated with T1 and reduced to almost nothing in the Rescue samples. A similar pattern was seen with TSP-1, where TSP-1 expression following "rescue" was decreased considerably. Overall, this data is in agreement with our previous observations that T3 has a significant non-fibrotic effect on HCFs, and presents a novel model for the "rescue" of both cellular and matrix fibrotic components with a single growth factor.
Yanai R, Mulki L, Hasegawa E, Takeuchi K, Sweigard H, Suzuki J, Gaissert P, Vavvas DG, Sonoda K-H, Rothe M, Schunck W-H, Miller JW, Connor KM. Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization. Proc Natl Acad Sci U S A 2014;111(26):9603-8.Abstract
Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)-epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD.
Pasquale LR, Kang JH, Wiggs JL. Prospects for gene-environment interactions in exfoliation syndrome. J Glaucoma 2014;:S64-7.Abstract

Complex traits can be triggered by environmental factors in genetically predisposed individuals. The lysyl oxidase-like 1 gene (LOXL1) variants associated with exfoliation syndrome (XFS) are detected in >90% of cases that have been genotyped from sites around the world. Remarkably, roughly 80% of people without XFS also possess these same variants in all populations that have been tested. Nonetheless, the prevalence of XFS varies from ≤0.4% to >20%. These data suggest that other genetic variants, epigenetic modifications, or environmental factors also contribute to XFS. Furthermore, it is possible that environmental factors modify the association between LOXL1 and XFS. Interactions between LOXL1 variants and environmental factors could explain the varying prevalence of XFS seen throughout the world. At the very least, the discovery of the association between LOXL1 variants and XFS has opened the door to the discovery of environmental risk factors for this condition. Candidate gene-environment interactions in XFS will be discussed.

Schroedl F, Kaser-Eichberger A, Schlereth SL, Bock F, Regenfuss B, Reitsamer HA, Lutty GA, Maruyama K, Chen L, Lütjen-Drecoll E, Dana R, Kerjaschki D, Alitalo K, De Stefano ME, Junghans BM, Heindl LM, Cursiefen C. Consensus statement on the immunohistochemical detection of ocular lymphatic vessels. Invest Ophthalmol Vis Sci 2014;55(10):6440-2.Abstract

There is currently considerable controversy about existence and classification of "lymphatic vessels" in the eye. Some of the confusion is certainly caused by inappropriate use (or nonuse) of the correct immunohistochemical markers. Many experts in the field expressed the need for a consensus statement, and, in this perspective, authors offer arguments and solutions to reliably continue with immunohistochemical ocular lymphatic research.

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