Transactions of the American Ophthalmological Society最新文献

{"title":"Erratum: The Hematologic Definition of Monoclonal Gammopathy of Undetermined Significance in Relation to Paraproteinemic Keratopathy (An American Ophthalmological Society Thesis).","authors":"Walter Lisch,&nbsp;Joanna Wasielica-Poslednik,&nbsp;Tero Kivelä,&nbsp;Ursula Schlötzer-Schrehardt,&nbsp;Jens M Rohrbach,&nbsp;Walter Sekundo,&nbsp;Uwe Pleyer,&nbsp;Christina Lisch,&nbsp;Alexander Desuki,&nbsp;Heidi Rossmann,&nbsp;Jayne S Weiss","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>[This corrects the article on p. T7 in vol. 114, PMID: 28050052.].</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333982/pdf/1545_6110-v114-t7c1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34783901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroanatomic Variations in Graves' Dysthyroid Ophthalmopathy as Studied With MRI.","authors":"Rona Z Silkiss,&nbsp;Alex R Wade","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether patients with Graves' dysthyroid ophthalmopathy (GDO) have changes in brain anatomy that can be assessed by neuroimaging as compared to age-matched controls.</p><p><strong>Methods: </strong>We examined 10 female, euthyroid patients with GDO and 14 age and gender matched controls using high-resolution structural MRI scanning. An automatic cortical segmentation algorithm was used to estimate the thickness of each subject's gray matter across the brain. The resulting cortical thickness measurements were transferred to a standard reference space via a template-based warping procedure. A statistical analysis of between-group cortical thickness differences using a general linear model with a combination of cluster-based and bootstrapped corrections for multiple comparisons was performed.</p><p><strong>Results: </strong>Patients with GDO have statistically significant thinning of the gray matter sheet in a minimum of eight locations: six in the right hemisphere (insula, paracentral, precuneus, superior frontal cingulate, superioparietal and postcentral) and two in the left hemisphere (lateral occipital sulcus, fusiform gyrus). Left hemisphere thinning occurred in portions of the occipital lobe while right hemisphere thinning occurred in a set of frontal and parietal areas known to be involved in self-evaluation and emotional and cognitive regulation.</p><p><strong>Conclusion: </strong>Patients with GDO exhibit localized changes in gray matter thickness. These changes may be associated with cognitive changes reported by GDO patients. Further research before and after treatment with larger patient cohorts and experimental protocols including psychiatric evaluation and functional MRI are recommended.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444882/pdf/1545_6110-v114-t9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35065278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease: Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis).","authors":"Shahzad I Mian,&nbsp;Paola De la Parra-Colín,&nbsp;Rafael De Melo-Franco,&nbsp;Christopher Johnson,&nbsp;Tonatiuh Barrientos-Gutierrez","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To determine if chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with stable or progressive dry eye disease and to determine the true incidence in patients with no prior history of dry eye disease.</p><p><strong>Methods: </strong>A nonconcurrent cohort study at a single institution with 136 patients who had no previous history of dry eye disease before HSCT. Survival analysis was used to estimate dry eye disease incidence. The incidence rate was calculated using life tables as the number of observed dry eye disease cases divided by the person-time at risk accumulated by the cohort. Transition probabilities were calculated from time of transplant to time of diagnosis, and then to last recorded visit.</p><p><strong>Results: </strong>Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the population at risk developed dry eye disease during the first 10 months post transplant. Time to develop dry eye disease was 2.5 months for mild dry eye disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis.</p><p><strong>Conclusions: </strong>Our findings suggest that dry eye disease associated with cGVHD is an extremely frequent event and shows a wide spectrum of severity, with a mild form presenting early and a moderate to severe form presenting later after HSCT. These findings need to be studied further to elucidate if these are two different pathophysiological entities or just different expressions of the same pathology.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692327/pdf/1545_6110-v113-t11.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34744144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carrier frequency of CYP1B1 mutations in the United States (an American Ophthalmological Society thesis).","authors":"Janey L Wiggs,&nbsp;Anne M Langgurth,&nbsp;Keri F Allen","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>CYP1B1 mutations cause autosomal recessive congenital glaucoma. Disease risk assessment for families with CYP1B1 mutations requires knowledge of the population mutation carrier frequency. The purpose of this study is to determine the CYP1B1 mutation carrier frequency in clinically normal individuals residing in the United States. Because CYP1B1 mutations can exhibit variable expressivity, we hypothesize that the mutation carrier frequency is higher than expected.</p><p><strong>Methods: </strong>Two hundred fifty individuals without glaucoma or a family history of glaucoma were enrolled. CYP1B1 mutations were identified by DNA sequencing, and pathogenicity was estimated by PolyPhen-2 or a previous report of disease causality.</p><p><strong>Results: </strong>Based on the disease frequency (1 in 10,000) and prevalence of CYP1B1-related congenital glaucoma (15% to 20%), the frequency of CYP1B1-related congenital glaucoma in the United States is approximately 1 in 50,000. Assuming Hardy-Weinberg equilibrium, the expected CYP1B1 mutation carrier frequency would be 1 in 112, or 0.89%. Among the 250 study participants, 11 (4.4%) are carriers of a single pathogenic mutation, representing a carrier frequency of 1 in 22, which is 5.1 times the expected frequency. A higher-than-expected carrier frequency (1 in 33, 3.0%) was also observed in 4300 white individuals sequenced by the National Heart Lung and Blood Institute Exome Sequencing Project.</p><p><strong>Conclusions: </strong>Our results show that the CYP1B1 mutation carrier frequency in the US population is between 1 in 22 and 1 in 33, which is 5.1 to 3.4 times the expected frequency. These results suggest that more individuals than expected are carriers of a deleterious CYP1B1 mutation, and that the prevalence of CYP1B1-related disease may be higher than expected.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311669/pdf/1545-6110_v112_p094.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33349395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical coherence tomographic and visual results at six months after transitioning to aflibercept for patients on prior ranibizumab or bevacizumab treatment for exudative age-related macular degeneration (an American Ophthalmological Society thesis).","authors":"Clement K Chan,&nbsp;Atul Jain,&nbsp;Srinivas Sadda,&nbsp;Neeta Varshney","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To study optical coherence tomographic (OCT) results and vision at 6 months after transition (post-Tx) from intravitreal bevacizumab and/or ranibizumab to aflibercept for treatment of neovascular age-related macular degeneration (nAMD). The null hypothesis was the lack of improvements in OCT metrics and vision outcome in study eyes at 6 months after transitioning from bevacizumab or ranibizumab to aflibercept.</p><p><strong>Methods: </strong>This retrospective study assessed 6 monthly OCT (Cirrus) data after transitioning to aflibercept for eyes on prior Legacy-ranibizumab, Legacy-bevacizumab, or mixed treatment for nAMD. Outcome measures were subretinal fluid (SRF), cystoid macular edema (CME), pigment epithelial detachment (PED) heights and volumes, central 1- and 3-mm subfield, Macular Volume, and best spectacle and pinhole visual acuity (VA). A single masked investigator performed all OCT measurements.</p><p><strong>Results: </strong>One hundred eighty-nine eyes in 172 patients in Legacy-bevacizumab (95 eyes), Legacy-ranibizumab (84 eyes), or Mixed Group(10 eyes) were switched to aflibercept and followed for 6 months. Significant post-Tx reductions were noted in SRF/CME heights and volumes (all P<.001). Similar findings were noted for PED heights (122.8 μm vs 79.4 μm) and PED volumes (all P<.001). Post-Tx VA was better (20/43 vs 20/51, P<.001). There were no differences between Legacy-bevacizumab and Legacy-ranibizumab groups in OCT and VA changes. Post-Tx VA, SRF/CME, and PED heights and volumes were improved for Nonresponders (suboptimal response to bevacizumab/ranibizumab) (P=.001 to <.001), but not Responders (good responses to same). The only adverse event was a retinal pigment epithelial tear in one eye.</p><p><strong>Conclusions: </strong>Significant improvements in vision and OCT metrics developed in Nonresponders but not in Responders. Post-Tx VA and OCT measures were similar for eyes on prior bevacizumab or ranibizumab. Post-Tx adverse events were uncommon.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307397/pdf/1545-6110_v112_p160.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33349400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of tuberin enhances photoreceptor survival and function in a preclinical model of retinitis pigmentosa (an american ophthalmological society thesis).","authors":"Stephen H Tsang,&nbsp;Lawrence Chan,&nbsp;Yi-Ting Tsai,&nbsp;Wen-Hsuan Wu,&nbsp;Chun-Wei Hsu,&nbsp;Jin Yang,&nbsp;Joaquin Tosi,&nbsp;Katherine J Wert,&nbsp;Richard J Davis,&nbsp;Vinit B Mahajan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the functional consequences of silencing of tuberin, an inhibitor of the mTOR signaling pathway, in a preclinical model of retinitis pigmentosa (RP) in order to test the hypothesis that insufficient induction of the protein kinase B (PKB)-regulated tuberin/mTOR self-survival pathway initiates apoptosis.</p><p><strong>Methods: </strong>In an unbiased genome-scale approach, kinase peptide substrate arrays were used to analyze self-survival pathways at the onset of photoreceptor degeneration. The mutant Pde6b(H620Q)/Pde6b(H620Q) at P14 and P18 photoreceptor outer segment (OS) lysates were labeled with P-ATP and hybridized to an array of 1,164 different synthetic peptide substrates. At this stage, OS of Pde6b(H620Q)/Pde6b(H620Q) rods are morphologically normal. In vitro kinase assays and immunohistochemistry were used to validate phosphorylation. Short hairpin RNA (shRNA) gene silencing was used to validate tuberin's role in regulating survival.</p><p><strong>Results: </strong>At the onset of degeneration, 162 peptides were differentially phosphorylated. Protein kinases A, G, C (AGC kinases), and B exhibited increased activity in both peptide array and in vitro kinase assays. Immunohistochemical data confirmed altered phosphorylation patterns for phosphoinositide-dependent kinase-1 (PDK1), ribosomal protein S6 (RPS6), and tuberin. Tuberin gene silencing rescued photoreceptors from degeneration.</p><p><strong>Conclusions: </strong>Phosphorylation of tuberin and RPS6 is due to the upregulated activity of PKB. PKB/tuberin cell growth/survival signaling is activated before the onset of degeneration. Substrates of the AGC kinases in the PKB/tuberin pathway are phosphorylated to promote cell survival. Knockdown of tuberin, the inhibitor of the mTOR pathway, increased photoreceptor survival and function in a preclinical model of RP.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311672/pdf/1545-6110_v112_p103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33349396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective evaluation of subretinal vessel location in polypoidal choroidal vasculopathy (PCV) and response of hemorrhagic and exudative PCV to high-dose antiangiogenic therapy (an American Ophthalmological Society thesis).","authors":"Gregg T Kokame","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to determine the following: (1) Is polypoidal choroidal vasculopathy (PCV) a subretinal neovascular process, rather than a choroidal vascular anomaly? and (2) Is a higher dose of ranibizumab (2.0 mg/0.05 mL) more effective in treating PCV than the current dose (0.5 mg/0.05 mL) approved for treatment of age-related macular degeneration?</p><p><strong>Methods: </strong>Retrospective evaluation of PCV in 104 eyes of 86 patients was accomplished with use of indocyanine green angiography plus optical coherence tomography to localize the branching vascular network and the polyps. Nineteen eyes of 19 patients with active leaking and exudation underwent a prospective open-label trial of monthly high-dose intravitreal ranibizumab (2.0 mg/0.05 mL). The primary outcome was prevention of major vision loss (≤15 ETDRS letters). Secondary outcomes included adverse events, improved vision, and changes in subretinal hemorrhage, subretinal fluid, macular edema, and polypoidal complexes at 6 months.</p><p><strong>Results: </strong>The PCV vessels were localized beneath the retinal pigment epithelium (RPE) and above Bruch's membrane in 103 (99%) of 104 eyes. In the high-dose ranibizumab trial at 6 months, none of the patients lost ≥15 letters in visual acuity, and 5 (26%) of 19 gained ≥15 letters. Decreases were noted in subretinal fluid in 14 (82%) of 17 eyes, subretinal hemorrhage in 12 (100%) of 12, RPE detachment in 14 (88%) of 16, macular edema in 11 (92%) of 12, and polyps in 15 (79%) of 19 eyes.</p><p><strong>Conclusions: </strong>PCV vessels are a subtype of subretinal neovascularization located above Bruch's membrane and below RPE. High-dose ranibizumab (2.0 mg/0.05 mL) decreased exudation and hemorrhage and resulted in significant polyp regression, although branching vascular networks persisted.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307886/pdf/1545-6110_v112_p074.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33024548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro studies on the antimicrobial peptide human beta-defensin 9 (HBD9): signalling pathways and pathogen-related response (an American Ophthalmological Society thesis).","authors":"Harminder S Dua,&nbsp;Ahmad Muneer Otri,&nbsp;Andrew Hopkinson,&nbsp;Imran Mohammed","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Human β-defensins (HBDs) are an important part of the innate immune host defense at the ocular surface. Unlike other defensins, expression of HBD9 at the ocular surface is reduced during microbial infection, but activation of toll-like receptor 2 (TLR2) in corneal epithelial cells has been shown to up-regulate HBD9. Our purpose was to test the hypothesis that TLR2 has a key role in the signalling pathway(s) involved in the overexpression or underexpression of HBD9, and accordingly, different pathogens would induce a different expression pattern of HBD9.</p><p><strong>Methods: </strong>The in vitro RNAi silencing method and response to dexamethasone were used to determine key molecules involved in signalling pathways of HBD9 in immortalized human corneal epithelial cells. The techniques included cell culture with exposure to specific transcription factor inhibitors and bacteria, RNA extraction and cDNA synthesis, quantitative real-time polymerase chain reaction, and immunohistology.</p><p><strong>Results: </strong>This study demonstrates that TLR2 induces HBD9 mRNA and protein expression in a time- and dose-dependent manner. Transforming growth factor-β-activated kinase 1 (TAK1) plays a central role in HBD9 induction by TLR2, and transcription factors c-JUN and activating transcription factor 2 are also involved. Dexamethasone reduces TLR2-mediated up-regulation of HBD9 mRNA and protein levels in mitogen-activated protein kinase phosphatase 1 (MKP1)-dependent and c-JUN-independent manner. HBD9 expression differs with gram-negative and gram-positive bacteria.</p><p><strong>Conclusions: </strong>TLR2-mediated MKPs and nuclear factor-κB signalling pathways are involved in HBD9 expression. TAK-1 is a key molecule. These molecules can be potentially targeted to modulate HBD9 expression. Differential expression of HBD9 with different bacteria could be related to differences in pathogen-associated molecular patterns of these organisms.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311673/pdf/1545-6110_v112_p050.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33349394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal pigment epithelial tears in the era of intravitreal pharmacotherapy: risk factors, pathogenesis, prognosis and treatment (an American Ophthalmological Society thesis).","authors":"David Sarraf,&nbsp;Anthony Joseph,&nbsp;Ehsan Rahimy","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the risk factors, pathogenesis, and prognosis of retinal pigment epithelial (RPE) tears and to demonstrate our hypothesis that continued anti-vascular endothelial growth factor (VEGF) therapy after an RPE tear has occurred correlates with improved long-term visual and anatomical outcomes.</p><p><strong>Methods: </strong>We searched a database of 10,089 patients and retrospectively identified a large case series of 56 eyes with neovascular age-related macular degeneration (AMD) complicated by an RPE tear over an 8-year period. Baseline visual acuity (VA) was tabulated and analysis of the RPE tear was performed with multimodal imaging. Follow-up VA, progression of the tear, and severity of fibrosis were evaluated, and each was correlated with number of anti-VEGF injections.</p><p><strong>Results: </strong>Average follow-up for the 56 eyes was 42 months, and mean logMAR VA at baseline was 0.88 (Snellen VA 20/150) with minimal decline over 3 years. LogMAR VA plotted against number of anti-VEGF injections demonstrated that more frequent and cumulative injections correlated with better VA (P<.0001). A greater number of anti-VEGF injections was associated with minimal progression of the RPE tear, reduced fibrosis, and lower risk of a large, end-stage exudative disciform scar.</p><p><strong>Conclusions: </strong>Fifteen to 20% of vascularized pigment epithelial detachments (PEDs) may develop RPE tears after anti-VEGF therapy due to progressive contraction of the type 1 choroidal neovascular membrane in a PED at risk. Continued monitoring of RPE tears for exudative changes warranting anti-VEGF therapy may stabilize VA, improve anatomical outcomes, reduce fibrosis, and decrease the risk of developing a large blinding end-stage exudative disciform scar.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310706/pdf/1545-6110_v112_p142.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33349398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid differentiation: the safety profile of various steroids on retinal cells in vitro and their implications for clinical use (an American Ophthalmological Society thesis).","authors":"Baruch D Kuppermann, Leandro Cabral Zacharias, M Cristina Kenney","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To determine if potentially viable alternatives to the clinical use of intravitreal triamcinolone acetonide should be considered based on a comparative assessment of the in vitro effects of five commercially available corticosteroids. We hypothesized that dexamethasone, betamethasone, methylprednisolone, loteprednol etabonate, and fluocinolone acetonide, at clinically relevant doses, may show different levels of in vitro cytotoxicity to retinal cells.</p><p><strong>Methods: </strong>Cultures of human retinal pigment epithelial cells (ARPE-19) and rat embryonal neurosensory precursor retinal cells (R28) were treated with dexamethasone, betamethasone, methylprednisolone, loteprednol, or fluocinolone acetonide. Cell viability as a measure of cell death was determined by trypan blue dye exclusion assay. The mechanical effect of drug crystals was evaluated by solubilizing the steroid formulations. Mitochondrial dehydrogenase and membrane potential were assessed to measure cell damage.</p><p><strong>Results: </strong>Betamethasone, loteprednol, and methylprednisolone, in commercially available forms, caused significant cytotoxic changes to retinal cells in vitro at clinically relevant doses. This effect was less pronounced with solubilized betamethasone. Dexamethasone at concentrations up to 5 times the clinical dose of free drug injections and 1000 times greater than a drug implant did not cause decreased cell viability. Fluocinolone acetonide at doses 1000 times higher than observed with drug delivery systems showed no cytotoxic effect.</p><p><strong>Conclusions: </strong>Betamethasone, loteprednol, and methylprednisolone exhibited cytotoxicity at clinically relevant doses and do not appear to be good therapeutic options for intravitreal use. In comparison, dexamethasone and fluocinolone acetonide, which exhibited fewer cytotoxic effects than other steroids, may be potentially viable alternatives to triamcinolone acetonide for clinical use.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311675/pdf/1545-6110_v112_p116.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33349397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}