Ophthalmology Commons^™

Postenucleation Adjuvant Chemotherapy With Vincristine, Etoposide, And Carboplatin For The Treatment Of High-Risk Retinoblastoma., Swathi Kaliki, Carol L Shields, Sanket U Shah, Ralph C Eagle, Jerry A Shields, Ann Leahey

Wills Eye Hospital Papers

BACKGROUND: Analysis of 52 eyes with high-risk retinoblastoma managed with postenucleation adjuvant chemotherapy using vincristine sulfate, etoposide phosphate, and carboplatin showed no evidence of systemic metastasis in any case during a mean (range) follow-up of 66 (12-202) months.

PURPOSE: To determine the efficacy of postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin in the prevention of metastasis for patients with high-risk retinoblastoma.

METHODS: Retrospective, nonrandomized, interventional case series of 52 eyes in 51 patients with high-risk retinoblastoma consisting of tumor invasion into the anterior segment, posterior uvea 3 mm or greater, postlaminar optic nerve, or any combination of posterior uvea …

Outcomes And Risk Factors Associated With Endophthalmitis After Intravitreal Injection Of Anti-Vascular Endothelial Growth Factor Agents., Chirag P Shah, Sunir J Garg, James F Vander, Gary C Brown, Richard S Kaiser, Julia A Haller, The Post-Injection Endophthalmitis (Pie) Study Team

Wills Eye Hospital Papers

OBJECTIVE: To describe outcomes of and risk factors for endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injection.

DESIGN: Single-center, consecutive, case series and retrospective case-control study.

PARTICIPANTS: Between January 1, 2009, and May 31, 2010, 16 vitreoretinal surgeons administered a total of 27 736 injections. During this period, 23 cases of presumed infectious endophthalmitis occurred. Each surgeon used his own preferred injection technique.

INTERVENTION: Vitreous or aqueous tap, or both, with intravitreal antibiotic injection and subsequent topical antibiotic and steroid drops.

MAIN OUTCOME MEASURES: Visual acuity, bladed lid speculum use, conjunctival displacement, hemisphere of injection, bevacizumab versus ranibizumab, and …

Ccr3 Inhibition For Ocular Angiogenesis And Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of inhibitors of the CCR3 receptor or its ligands eotaxin (CCL11), eotaxin-2 (CCL24) or eotaxin-3 (CCL26) inhibits ocular angiogenesis.

P2-498 Parents' Perceptions And Practices Regarding Consanguinity Related To Β-Thalassaemia: A Matched Case Control Study, M Beg, R Siddiqui, Khabir Ahmad, Khadija Humayun

Department of Surgery

introduction b-thalassaemia is most common genetically transmitted disorder in Eastern Mediterranean region including Pakistan. Like other recessive disorders, prevalence increases through consanguinity; Pakistan Demographic and Health Survey reports 50% consanguineous marriages. Perceptions about consanguinity in our population have recently not been studied. Objectives were to determine consanguinity related characteristics among parents of children with thalassaemia and without thalassaemia visiting a major health centre in Karachi-Pakistan. To compare consanguinity practices among such families and to assess susceptibility, benefits and barriers towards thalassaemia. Methods Sample of 340 cases and 340 controls; age-sex matched were selected from February to April 2010. Parents of …

Importance Of Proper Diagnosis For Management: Multifocal Choroiditis Mimicking Ocular Histoplasmosis Syndrome., Elham Hatef, Peykan Turkcuoglu, Mohamed Ibrahim, Yasir J. Sepah, Matthew Shulman, Jangwon Heo, Jeong H. Lee, Roomasa Channa, Afsheen Khwaja, Zubir Rentiya, Syed Mahmood Shah, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

PURPOSE: The study aims to evaluate a series of patients with initial diagnosis of ocular histoplasmosis syndrome (OHS) with progression and response to treatments consistent with multifocal choroiditis (MFC).

METHODS: Retrospective review of nine patients referred for management of recurrent OHS lesions. Serology panel was conducted to rule out autoimmune and infectious causes.

RESULTS: Clinical examination revealed multiple small, punched-out peripheral chorioretinal scars, and peripapillary atrophy. Histoplasma antigen/antibody was negative in all patients. Fluorescein angiography and optical coherence tomography confirmed active inflammation in five patients. Immunomodulatory therapy (IMT) was initiated to control active inflammation. While on IMT, visual acuity stabilized …

Primary School Vision Screening Involving Teachers In Nampula, Mozambique, Aoife Phelan, Lisa O'Donoghue, Kathryn Saunders, Stephen Thompson, Vivien Ocampo, Kevin Naidoo, James Loughman

Conference Papers

Purpose: There is no plan for a national child eye care programme or existing human resource infrastructure to address the immediate challenge of child eye health in Mozambique.This study aims to design, implement and evaluate a school based pediatric vision screening service, to identify those in need of eye care services, among Mozambique’s 11,561,000 children.

Methods: Primary School Screening took place in three schools in Nampula, Mozambique in September 2010 and March 2011. The children’s vision was screened by an optometry student, optometrist or teacher with Log MAR ETDRS letters at 4 Meters. Ophthalmoscopy was performed on all children by …

A Positive Feedback Synapse From Retinal Horizontal Cells To Cone Photoreceptors., Skyler L. Jackman, Norbert Babai, James J. Chambers, Wallace B. Thoreson, Richard H. Kramer

Journal Articles: Ophthalmology

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca(2+) and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca(2+), whereas negative feedback is mediated by a change in HC membrane …

Transplantation Of Adult Mouse Ips Cell-Derived Photoreceptor Precursors Restores Retinal Structure And Function In Degenerative Mice, Budd A. Tucker, In-Hyun Park, Sara D. Qi, Henry J. Klassen, Caihui Jiang, Jing Yao, Stephen Redenti, George Q. Daley, Michael J. Young

Publications and Research

This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs), could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immunecompromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At …

Methods And Animal Model For Analyzing Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.

Quantal Amplitude At The Cone Ribbon Synapse Can Be Adjusted By Changes In Cytosolic Glutamate., Theodore M. Bartoletti, Wallace B. Thoreson

Journal Articles: Ophthalmology

PURPOSE: Vision is encoded at photoreceptor synapses by the number of released vesicles and size of the post-synaptic response. We hypothesized that elevating cytosolic glutamate could enhance quantal size by increasing glutamate in vesicles.

METHODS: We introduced glutamate (10-40 mM) into cone terminals through a patch pipette and recorded excitatory post-synaptic currents (EPSCs) from horizontal or OFF bipolar cells in the Ambystoma tigrinum retinal slice preparation.

RESULTS: Elevating cytosolic glutamate in cone terminals enhanced EPSCs as well as quantal miniature EPSCs (mEPSCs). Enhancement was prevented by inhibiting vesicular glutamate transport with 1S,3R-1-aminocyclopentane-1,3-dicarboxylate in the patch pipette. A low affinity glutamate …

Lateral Mobility Of Presynaptic L-Type Calcium Channels At Photoreceptor Ribbon Synapses., Aaron J. Mercer, Minghui Chen, Wallace B. Thoreson

Journal Articles: Ophthalmology

At most synapses, presynaptic Ca(2+) channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. We examined the lateral membrane mobility of presynaptic L-type Ca(2+) channels at photoreceptor ribbon synapses of the tiger salamander (Ambystoma tigrinum) retina. Movements of individual Ca(2+) channels were tracked by coupling quantum dots to an antibody against the extracellular α(2)δ(4) Ca(2+) channel subunit. α(2)δ(4) antibodies labeled photoreceptor terminals and colocalized with antibodies to synaptic vesicle glycoprotein 2 and voltage-gated Ca(2+) channel 1.4 (Ca(V)1.4) α(1) subunits. The results show that Ca(2+) channels are dynamic and move within a confined region beneath the …

Chloroquine Treatment Of Arpe-19 Cells Leads To Lysosome Dilation And Intracellular Lipid Accumulation: Possible Implications Of Lysosomal Dysfunction In Macular Degeneration, Patrick M. Chen, Zoë J. Gombart, Jeff W. Chen

Dartmouth Scholarship

Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly people over 60. The pathogenesis is still unclear. It has been suggested that lysosomal stress may lead to drusen formation, a biomarker of AMD. In this study, ARPE-19 cells were treated with chloroquine to inhibit lysosomal function. Chloroquine-treated ARPE-19 cells demonstrate a marked increase in vacuolation and dense intracellular debris. These are identified as chloroquine-dilated lysosomes and lipid bodies with LAMP-2 and LipidTOX co-localization, respectively. Dilation is an indicator of lysosomal dysfunction. Chloroquine disrupts uptake of exogenously applied rhodamine-labeled dextran by these cells. This suggests a disruption …

Photodisruption In Ocular Tissue Near And At The Boundary Between The Anterior Chamber And Crystalline Lens, Richard Ty Olmstead

Electronic Theses and Dissertations

Lasers have been involved in Ophthalmology in the treatment of myopia and hyperopia for several years. Laser systems have transformed patients‟ quality of life, freeing them from the need for glasses, as in the case of LASIK. Ultrafast lasers have played an important role in surgery of the eye. In LASIK, they are used to cut the flap that is lifted to expose the stroma for UV Excimer laser treatment of this region. They are now being used for surgery deeper into the eye,for instance, treating the lens as part of treatments for cataract surgery. The use of ultrafast lasers …

Variability In Short-Wavelength Automated Perimetry Among Peri- Or Postmenopausal Women: A Dependence On Phyto-Oestrogen Consumption?, Alvin Eisner, Shaban Demirel

Community Health Faculty Publications and Presentations

Purpose:  To determine whether the hill of vision for Short-Wavelength Automated Perimetry (SWAP) is shallower for women who consume phyto-oestrogen-rich foods than for women who do not.

Methods:  Visual field data were compared for two groups of healthy amenorrhoeic women 48–69 years-old with normal vision and not using hormone replacement: (1) 24 subjects who reported consuming soy and/or flax products and (2) 20 subjects who reported not consuming these products. Two types of 24-2 visual fields were measured: (1) Full Threshold SWAP and (2) a white-on-white (W/W) field obtained using a Swedish Interactive Threshold Algorithm (SITA Standard).

Results:  The reduction …

Psychophysical Impact And Optical And Morphological Characteristics Of Symptomatic Non-Advanced Cataract., James Loughman, S. Charalampidou, J. Nolan, J. Stack, G. Higgins, L. Cassidy, S. Beatty

Articles

To investigate whether psychophysical, morphological, and/or optical characteristics of symptomatic non-advanced cataract are complementary to, or more appropriate than, visual acuity (VA) for the purposes of recording visual data that reflect subjective visual difficulty in patients with cataract that exhibit relative sparing of high contrast acuity (0.4 logarithm of minimal angle of resolution (logMAR) scale or better). Methods Eighty-two patients with symptomatic non-advanced cataract and no other ocular pathology were asked to complete a validated questionnaire, and to perform a series of visual function assessments including: corrected distance VA (CDVA); photopic and mesopic contrast sensitivity; photopic and mesopic glare disability …

Breast Cancer Medications And Vision: Effects Of Treatments For Early-Stage Disease, Alvin Eisner, Shiuh-Wen Luoh

Community Health Faculty Publications and Presentations

This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve …

One Student One Family And The Mozambique Eyecare Project, Stephen Thompson, Aoife Phelan, Tatiana Santana, Elizebete Catarino, Vivien Ocampo, Cesar Faria, James Loughman

Articles

Background - The Mozambique Eyecare Programme is funded by Irish Aid and designed to address the need for optometric education in Lusophone Africa. It is a multi-partner collaboration between Universidade Lúrio, Mozambique, Technological University Dublin, Ireland, University of Ulster, Northern Ireland, and The International Centre for Eyecare Education (ICEE) an international Non Government Organisation. A key output from the programme is the development of an optometry school based at Universidade Lúrio, the first of its kind in Mozambique. The aim is to address unmet eye care needs through human resource development.

All students enrolled at Universidade Lúrio, including the optometry …

Significant Inhibition Of Corneal Scarring In Vivo With Tissue-Selective, Targeted Aav5 Decorin Gene Therapy, Rajiv R. Mohan, Ashish Tandon, Ajay Sharma, John W. Cowden, Jonathan C. K. Tovey

Pharmacy Faculty Articles and Research

PURPOSE. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the stroma with adeno-associated virus serotype 5 (AAV5) inhibits corneal fibrosis in vivo without significant side effects.

METHODS. An in vivo rabbit model of corneal fibrosis was used. Targeted decorin gene therapy was delivered to the rabbit cornea by a single topical application of AAV5 (100 L; 6.5 1012 g/mL) onto the bare stroma for 2 minutes. The levels of corneal fibrosis were determined with stereomicroscopy, slit lamp biomicroscopy, -smooth muscle actin ( SMA), fibronectin, and F-actin immunocytochemistry, and/or immunoblotting. CD11b, F4/80 immunocytochemistry, and TUNEL assay …

Targeted Decorin Gene Therapy Delivered With Adeno-Associated Virus Effectively Retards Corneal Neovascularization In Vivo, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Gregory S. Schultz, John W. Cowden, Ashish Tandon

Pharmacy Faculty Articles and Research

Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 μl; 5x10^12 vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and …

Polyethylenimine-Conjugated Gold Nanoparticles: Gene Transfer Potential And Low Toxicity In The Cornea, Ajay Sharma, Ashish Tandon, Jonathan C. K. Tovey, Rangan Gupta, J. David Robertson, Jennifer A. Fortune, Alexander M. Klibanov, John W. Cowden, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNP) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNP with nitrogen-to-phosphorus (N/P) ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNP applied to corneal tissues collected after 12 h, 72 h, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNP over time. Transmission electron microscopy detected GNP in the keratocytes and the extracellular matrix of the rabbit corneas. …

Efficacious And Safe Tissue-Selective Controlled Gene Therapy Approaches For The Cornea, Rajiv R. Mohan, Sunilima Sinha, Ashish Tandon, Rangan Gupta, Jonathan C. K. Tovey, Ajay Sharma

Pharmacy Faculty Articles and Research

Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5), and a minimally invasive hair-dryer based vector-delivery technique were used. Fifty microliters of AAV5 titer (6.561012 vg/ml) expressing green fluorescent protein gene (GFP) was topically applied onto normal or diseased (fibrotic or neovascularized) rabbit corneas for 2-minutes with a custom vector-delivery technique. Corneal fibrosis and neovascularization in rabbit …