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VanderVeen DK, Nizam A, Lynn MJ, Bothun ED, McClatchey SK, Weakley DR, DuBois LG, Lambert SR, Lambert SR. Predictability of intraocular lens calculation and early refractive status: the Infant Aphakia Treatment Study. Arch Ophthalmol 2012;130(3):293-9.Abstract
OBJECTIVE: To report the accuracy of intraocular lens (IOL) power calculations and the early refractive status in pseudophakic eyes of infants in the Infant Aphakia Treatment Study. METHODS: Eyes randomized to receive primary IOL implantation were targeted for a postoperative refraction of +8.0 diopters (D) for infants 28 to 48 days old at surgery and +6.0 D for those 49 days or older to younger than 7 months at surgery using the Holladay 1 formula. Refraction 1 month after surgery was converted to spherical equivalent, and prediction error (PE; defined as the calculated refraction minus the actual refraction) and absolute PE were calculated. Baseline eye and surgery characteristics and A-scan quality were analyzed to compare their effect on PE. MAIN OUTCOME MEASURES: Prediction error. RESULTS: Fifty-six eyes underwent primary IOL implantation; 7 were excluded for lack of postoperative refraction (n = 5) or incorrect technique in refraction (n = 1) or biometry (n = 1). Overall mean (SD) absolute PE was 1.8 (1.3) D and mean (SD) PE was +1.0 (2.0) D. Absolute PE was less than 1 D in 41% of eyes but greater than 2 D in 41% of eyes. Mean IOL power implanted was 29.9 D (range, 11.5-40.0 D); most eyes (88%) implanted with an IOL of 30.0 D or greater had less postoperative hyperopia than planned. Multivariate analysis revealed that only short axial length (<18 mm) was significant for higher PE. CONCLUSIONS: Short axial length correlates with higher PE after IOL placement in infants. Less hyperopia than anticipated occurs with axial lengths of less than 18 mm or high-power IOLs. Application to Clinical Practice Quality A-scans are essential and higher PE is common, with a tendency for less hyperopia than expected. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00212134.
Sullivan DA, Hammitt KM, Schaumberg DA, Sullivan BD, Begley CG, Gjorstrup P, Garrigue J-S, Nakamura M, Quentric Y, Barabino S, Dalton M, Novack GD. Report of the TFOS/ARVO Symposium on global treatments for dry eye disease: an unmet need. Ocul Surf 2012;10(2):108-16.Abstract
In September 2010, a Symposium in Florence, Italy, was held to address the unmet need for global treatments for dry eye disease (DED). It was sponsored by The Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and co-sponsored by the Association for Research in Vision & Ophthalmology (www.arvo.org). The Symposium objectives were two-fold: first, to discuss accepted and emerging clinical endpoints of DED with regulatory experts from around the world; and second, to consider how to improve clinical trials of treatments for DED. The Symposium focused on the personal and collective burden of DED, as well as the developmental and regulatory challenges associated with generating new DED therapeutics. This article provides a synopsis of many of the presentations, discussions and recommendations of this Symposium.
Singh G, Robinson CM, Dehghan S, Schmidt T, Seto D, Jones MS, Dyer DW, Chodosh J. Overreliance on the hexon gene, leading to misclassification of human adenoviruses. J Virol 2012;86(8):4693-5.Abstract
The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences with identical hexon genes, which were the same as the one previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss coinfections. Whole-genome sequencing remains the gold standard for proper classification of HAdVs.
Shazly TA, Latina MA. Use of processed pericardium graft to plug patulous old sclerostomy track during glaucoma shunt revision for exposure. Ophthalmic Surg Lasers Imaging 2012;43(1):72-5.Abstract
The authors demonstrate a reproducible technique using processed pericardium to seal sclerostomy track during glaucoma shunt revision. The suggested method involves placement of a wedge-shaped processed pericardial graft into the old sclerostomy tract following tube explantation. The graft is trimmed and sutured to the sclera. The tube is reinserted into a new sclerostomy and then sutured in place and covered in the usual fashion. This method allowed relatively easy treatment of three patients with patulous sclerostomy with necrotic edges. A successful tube revision and repositioning of the tube using this technique was performed on three patients with exposed tubes. The intraocular pressure was between 8 and 12 mm Hg from postoperative day 1. The authors suggest the use of pericardium plug to adequately seal the old sclerostomy track during glaucoma shunt revision. The plug allows tube repositioning at a new site without the need to suture the friable sclerostomy edges.
Yiu G, Lessell S. Dorsal midbrain syndrome from a ring-enhancing lesion. Semin Ophthalmol 2012;27(3-4):65-8.Abstract
A ring-enhancing lesion is an uncommon cause of a dorsal midbrain syndrome. Here, we describe the case of a 60-year-old man with eye movement and pupillary findings consistent with dorsal midbrain syndrome, and in whom neuroimaging showed a single ring-enhancing lesion in the right midbrain and thalamus. Further investigation revealed a longstanding right groin mass which proved to be a malignant melanoma. His intracranial lesion was presumed to be a metastatic lesion, and treated with stereotactic radiosurgery. We report the patient's clinical course, and discuss the diagnosis and management of the solitary midbrain lesion.
Wong JJ, Chen TC, Shen LQ, Pasquale LR. Macular imaging for glaucoma using spectral-domain optical coherence tomography: a review. Semin Ophthalmol 2012;27(5-6):160-6.Abstract
Since its introduction, optical coherence tomography (OCT) has become widely used and accepted as an imaging modality to detect and follow glaucoma, with measurement of the peripapillary retinal nerve fiber layer (pRNFL) being the most utilized parameter. Up until recently, macular thickness parameters have not been commonly used in glaucoma due to results of earlier studies with time-domain OCT (TD-OCT) that revealed macular imaging to be inferior to pRNFL in the diagnosis of glaucoma. The recent advent of spectral-domain OCT (SD-OCT) has renewed interest in the potential uses of macular imaging in glaucoma due to its ability to better segment and measure individual retinal layers. Multiple studies have been performed in the last few years to investigate the diagnostic ability, reproducibility, and limitations of these new SD-OCT macular parameters. The purpose of this paper is to review the findings of those studies to assess the current utility of macular SD-OCT in glaucoma. Overall, SD-OCT has been shown to have higher reproducibility than TD-OCT, and though there have been some conflicting reports, the majority of studies seem to concur that the diagnostic sensitivity of SD-OCT macular parameters is at least comparable to TD-OCT and other SD-OCT parameters.
Wen X-H, Duda T, Pertzev A, Venkataraman V, Makino CL, Sharma RK. S100B serves as a Ca(2+) sensor for ROS-GC1 guanylate cyclase in cones but not in rods of the murine retina. Cell Physiol Biochem 2012;29(3-4):417-30.Abstract
Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca(2+) signal transduction switch. Lowering [Ca(2+)](i) from 200 to 20 nM progressively turns it "ON" as does raising [Ca(2+)](i) from 500 to 5000 nM. The mode operating at lower [Ca(2+)](i) plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca(2+)](i) is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca(2+)-sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K(1/2) for Ca(2+) greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where [Ca(2+)](i) levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in [Ca(2+)](i) in cone outer segments. The findings define a new cone-specific Ca(2+)-dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.
Vu KTH, Jager MJ, Chen DF. The Immunology of Glaucoma. Asia Pac J Ophthalmol (Phila) 2012;1(5):303-11.Abstract
The presence of specific antibodies and T cells that are specific in patients with glaucoma supports the idea that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy, at least in some patients. At present, our understanding regarding immunological mechanisms associated with glaucomatous optic neuropathy is far from satisfactory. In this review, we examined evidence suggesting involvement of autoimmune responses in the pathogenesis of glaucoma. These include detection of autoantibodies and T cells and expression of cytokines and stress proteins in patients with glaucoma. Although immune responses are thought to be detrimental, some responses may exert a protective effect against neurodegenerative damage. Likely, the balance between positive and negative regulators determines the survival or demise of cells. It is vital that research continues to elucidate the roles of the immune system in glaucomatous neurodegeneration and the possibility of alternative modalities of treatment. These studies may also provide valuable molecular biomarkers for the diagnosis and identification of a specific cohort of patients with glaucoma, that is, those with normal-tension glaucoma.
Park EY, Kazlauskas A. Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA). Biosci Rep 2012;32(4):393-400.Abstract
The plasma level of LPA (lysophosphatidic acid) (200-600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA.
Moskowitz A, Hansen RM, Eklund SE, Fulton AB. Electroretinographic (ERG) responses in pediatric patients using vigabatrin. Doc Ophthalmol 2012;124(3):197-209.Abstract
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.
Sayegh RR, Pineda R. Practical applications of anterior segment optical coherence tomography imaging following corneal surgery. Semin Ophthalmol 2012;27(5-6):125-32.Abstract
Anterior segment optical coherence tomography (AS-OCT) has recently emerged as an important modality for imaging of the cornea. Since its introduction less than a decade ago, it has been clinically used for the diagnosis and management of an expanding number of corneal conditions. In this review, we will discuss the applications of anterior segment optical coherence tomography after corneal surgery, focusing on penetrating and lamellar keratoplasty, keratoprosthesis, intracorneal ring segments, collagen cross-linking and refractive surgery. Anterior segment optical coherence tomography is useful in evaluating outcomes, detecting adverse events, determining prognosis, guiding management decisions, and surgical planning.
Liu Y, Biarnés Costa M, Gerhardinger C. IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation. PLoS One 2012;7(5):e36949.Abstract
Many molecular and cellular abnormalities detected in the diabetic retina support a role for IL-1β-driven neuroinflammation in the pathogenesis of diabetic retinopathy. IL-1β is well known for its role in the induction and, through autostimulation, amplification of neuroinflammation. Upregulation of IL-1β has been consistently detected in the diabetic retina; however, the mechanisms and cellular source of IL-1β overexpression are poorly understood. The aim of this study was to investigate the effect of high glucose and IL-1β itself on IL-1β expression in microglial, macroglial (astrocytes and Müller cells) and retinal vascular endothelial cells; and to study the effect of diabetes on the expression of IL-1β in isolated retinal vessels and on the temporal pattern of IL-1β upregulation and glial reactivity in the retina of streptozotocin-diabetic rats. IL-1β was quantified by RealTime RT-PCR and ELISA, glial fibrillar acidic protein, α2-macroglobulin, and ceruloplasmin by immunoblotting. We found that high glucose induced a 3-fold increase of IL-1β expression in retinal endothelial cells but not in macroglia and microglia. IL-1β induced its own synthesis in endothelial and macroglial cells but not in microglia. In retinal endothelial cells, the high glucose-induced IL-1β overexpression was prevented by calphostin C, a protein kinase C inhibitor. The retinal vessels of diabetic rats showed increased IL-1β expression as compared to non-diabetic rats. Retinal expression of IL-1β increased early after the induction of diabetes, continued to increase with progression of the disease, and was temporally associated with upregulation of markers of glial activation. These findings point to hyperglycemia as the trigger and to the endothelium as the origin of the initial retinal upregulation of IL-1β in diabetes; and to IL-1β itself, via autostimulation in endothelial and macroglial cells, as the mechanism of sustained IL-1β overexpression. Interrupting the vicious circle triggered by IL-1β autostimulation could limit the progression of diabetic retinopathy.
Sadaka A, Durand ML, Gilmore MS. Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: host-microbe interactions in intraocular infection. Prog Retin Eye Res 2012;31(4):316-31.Abstract
Bacterial endophthalmitis is a sight threatening infection of the interior structures of the eye. Incidence in the US has increased in recent years, which appears to be related to procedures being performed on an aging population. The advent of outpatient intravitreal therapy for management of age-related macular degeneration raises yet additional risks. Compounding the problem is the continuing progression of antibiotic resistance. Visual prognosis for endophthalmitis depends on the virulence of the causative organism, the severity of intraocular inflammation, and the timeliness of effective therapy. We review the current understanding of the pathogenesis of bacterial endophthalmitis, highlighting opportunities for the development of improved therapeutics and preventive strategies.
Kurbanyan K, Hoesl LM, Schrems WA, Hamrah P. Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study. Eye (Lond) 2012;26(1):126-32.Abstract
PURPOSE: To study sub-basal corneal nerve alterations in patients with acute Acanthamoeba keratitis (AK) and fungal keratitis (FK), using laser in vivo confocal microscopy (IVCM). METHODS: A retrospective analysis of IVCM (Heidelberg Retina Tomograph 3/Rostock Cornea Module) images of 10 AK corneas and 4 FK corneas was performed, and the results compared with those of 10 normal and 12 acute herpetic keratitis (HK) corneas. Sub-basal corneal nerves were analyzed with respect to total number of nerves, main nerve trunks, branching pattern and total length of nerves per image, as well as tortuosity. For each variable, results for three frames were averaged and analyzed using analysis of variance. RESULTS: Total corneal nerve length was significantly (P < 0.0001) reduced in patients with AK (193.4 ± 124.5 μm) and FK (268.6 ± 257.4 μm) when compared with normal controls (3811.84 ± 911.4 μm). Total nerve counts in patients with AK (3.9 ± 1.2) and FK (3.6 ± 3.2) were significantly (P < 0.0001) decreased in comparison with normal controls (24.7 ± 5.5). The number of main nerve trunks and nerve branching was found to be significantly lower in AK and FK corneas, when compared with controls. There was a statistically significant decrease in the above parameters when compared with HK controls. CONCLUSIONS: The sub-basal corneal nerve plexus is significantly diminished in eyes with AK and FK, as demonstrated by IVCM. These results are more profound than previously reported findings of a diminished nerve plexus in HK.

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