Transactions of the American Ophthalmological Society最新文献

{"title":"Postulating a role for connective tissue elements in inferior oblique muscle overaction (an American Ophthalmological Society thesis).","authors":"David Stager,&nbsp;Linda K McLoon,&nbsp;Joost Felius","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the localization and density of collagens I, IV, VI, and elastin, the major protein components of connective tissue, in the inferior oblique muscle of patients with overelevation in adduction and in controls and to characterize changes that develop following surgery. Biomechanical studies suggest that the connective tissue matrix plays a critical role in extraocular muscle function, determining tensile strength and force transmission during contraction.</p><p><strong>Methods: </strong>Prospective laboratory-based case-control study of inferior oblique muscle specimens from 31 subjects: 16 with primary inferior oblique overaction, 6 with craniofacial dysostosis, and 9 normal controls. Collagen I, IV, VI, and elastin were localized and quantified using immunohistochemical staining. Densities were compared using analysis of variance and post hoc comparisons.</p><p><strong>Results: </strong>In primary inferior oblique overaction, all connective tissue components in unoperated specimens were elevated compared to controls (P<.0001). Previously operated muscles showed normal levels of collagens IV and VI (P>.27) but increased collagen I. In unoperated craniofacial dysostosis specimens, only elastin was elevated (P=.03), whereas density of collagens IV and VI was lower in previously operated vs unoperated specimens (P=.015).</p><p><strong>Conclusions: </strong>Elevated collagen and elastin levels in the cohort with primary inferior oblique overaction are consistent with the clinical finding of muscle stiffness. Contrarily, normal connective tissue densities in craniofacial dysostosis support the hypothesis that overelevation in this group reflects anomalous muscle vectors rather than tissue changes. Surgical intervention was associated with changes in the connective tissue matrix in both cohorts. These results have ramifications for treating patients with overelevation in adduction.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":" ","pages":"119-32"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812716/pdf/1545-6110_v111_p119.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31996242","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":"Development of a new valid, reliable, and internationally applicable assessment tool of residents' competence in ophthalmic surgery (an American Ophthalmological Society thesis).","authors":"C Golnik, Hilary Beaver, Vinod Gauba, Andrew G Lee, Eduardo Mayorga, Gabriela Palis, George M Saleh","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To test the validity and reliability of a new tool for assessing residents' competence in ophthalmic surgery. Changing paradigms of ophthalmic education in the United States have influenced worldwide ophthalmic education and necessitated new methods of assessing resident competence. Accordingly, a new tool for assessing residents' competence in ophthalmic surgery (phacoemulsification) that could be applicable internationally was developed. We hypothesize that this instrument is valid and reliable.</p><p><strong>Methods: </strong>A panel of six international content experts adapted a previously published tool for assessing phacoemulsification. The tool (called the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric, or ICO-OSCAR:phaco) was reviewed by 12 international content experts for their constructive comments, which were incorporated to ensure content validity. Ten expert cataract surgery teachers then graded six recorded phacoemulsification surgeries with the ICO-OSCAR:phaco to investigate inter-rater reliability.</p><p><strong>Results: </strong>The coefficient alpha statistic (a measure of reliability/internal consistency) for the ICO-OSCAR:phaco as a whole was 0.92, and 17 of its 20 dimensions had alpha coefficients greater than 0.70.</p><p><strong>Conclusions: </strong>The ICO-OSCAR:phaco is a valid and reliable assessment tool that could be applied internationally to satisfy the global need of new instruments to comply with emerging trends in ophthalmic education. A toolbox of similar surgical competency assessment tools is being developed.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":" ","pages":"24-33"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783252/pdf/1545-6110_v111_p024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31764026","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 tomography-based corneal power measurement and intraocular lens power calculation following laser vision correction (an American Ophthalmological Society thesis).","authors":"David Huang,&nbsp;Maolong Tang,&nbsp;Li Wang,&nbsp;Xinbo Zhang,&nbsp;Rebecca L Armour,&nbsp;Devin M Gattey,&nbsp;Lorinna H Lombardi,&nbsp;Douglas D Koch","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To use optical coherence tomography (OCT) to measure corneal power and improve the selection of intraocular lens (IOL) power in cataract surgeries after laser vision correction.</p><p><strong>Methods: </strong>Patients with previous myopic laser vision corrections were enrolled in this prospective study from two eye centers. Corneal thickness and power were measured by Fourier-domain OCT. Axial length, anterior chamber depth, and automated keratometry were measured by a partial coherence interferometer. An OCT-based IOL formula was developed. The mean absolute error of the OCT-based formula in predicting postoperative refraction was compared to two regression-based IOL formulae for eyes with previous laser vision correction.</p><p><strong>Results: </strong>Forty-six eyes of 46 patients all had uncomplicated cataract surgery with monofocal IOL implantation. The mean arithmetic prediction error of postoperative refraction was 0.05 ± 0.65 diopter (D) for the OCT formula, 0.14 ± 0.83 D for the Haigis-L formula, and 0.24 ± 0.82 D for the no-history Shammas-PL formula. The mean absolute error was 0.50 D for OCT compared to a mean absolute error of 0.67 D for Haigis-L and 0.67 D for Shammas-PL. The adjusted mean absolute error (average prediction error removed) was 0.49 D for OCT, 0.65 D for Haigis-L (P=.031), and 0.62 D for Shammas-PL (P=.044). For OCT, 61% of the eyes were within 0.5 D of prediction error, whereas 46% were within 0.5 D for both Haigis-L and Shammas-PL (P=.034).</p><p><strong>Conclusions: </strong>The predictive accuracy of OCT-based IOL power calculation was better than Haigis-L and Shammas-PL formulas in eyes after laser vision correction.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":" ","pages":"34-45"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797831/pdf/1545-6110_v111_p034.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40272745","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":"Stimulating retinal blood vessel protection with hypoxia-inducible factor stabilization: identification of novel small-molecule hydrazones to inhibit hypoxia-inducible factor prolyl hydroxylase (an American Ophthalmological Society thesis).","authors":"Jonathan E Sears,&nbsp;George Hoppe","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To discover novel small molecules that inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD), a key enzyme that regulates the posttranslational stability and hence activity of HIF.</p><p><strong>Methods: </strong>NIH3T3 cell line stably transfected with firefly luciferase under a HIF-1-inducible promoter was used to screen a Chembridge library of 34,000 small molecules of molecular weight 250 to 550 Da. Positive hits were considered at 4.5-fold higher luminescence than control. Selected compounds were validated in vitro. The most effective dose was then used to treat mice expressing firefly luciferase fused to the oxygen-dependent degradation domain (lucODD) in order to determine the location of the receptor for systemic treatment with small-molecule HIF PHD inhibitors.</p><p><strong>Results: </strong>Twenty-three novel small molecules were discovered, the majority of which were hydrazones and hydrazines. Of the 23 compounds, each had different selectivity for expression of erythropoietin or vascular endothelial growth factor, two angiogenic, HIF-regulated gene products. In addition, each showed different selectivity for hepatocytes or kidney, or both or neither, when injected intraperitoneally in an in vivo reporter gene assay.</p><p><strong>Conclusion: </strong>The discovery of multiple small molecules that inhibit HIF PHD identifies new reagents to develop strategies to prevent the degradation of HIF by its selective PHD. These molecules are novel hypoxia mimetics that may provide new strategies to protect retinovasculature from hyperoxia.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":"111 ","pages":"169-79"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812904/pdf/1545-6110_v111_p169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9902870","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":"The blue arc entoptic phenomenon in glaucoma (an American ophthalmological thesis).","authors":"Louis R Pasquale,&nbsp;Steven Brusie","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether the blue arc entoptic phenomenon, a positive visual response originating from the retina with a shape that conforms to the topology of the nerve fiber layer, is depressed in glaucoma.</p><p><strong>Methods: </strong>We recruited a cross-sectional, nonconsecutive sample of 202 patients from a single institution in a prospective manner. Subjects underwent full ophthalmic examination, including standard automated perimetry (Humphrey Visual Field 24-2) or frequency doubling technology (Screening C 20-5) perimetry. Eligible patients viewed computer-generated stimuli under conditions chosen to optimize perception of the blue arcs. Unmasked testers instructed patients to report whether they were able to perceive blue arcs but did not reveal what response was expected. We created multivariable logistic regression models to ascertain the demographic and clinical parameters associated with perceiving the blue arcs.</p><p><strong>Results: </strong>In multivariable analyses, each 0.1 unit increase in cup-disc ratio was associated with 36% reduced likelihood of perceiving the blue arcs (odds ratio [OR] = 0.66 [95% confidence interval (CI): 0.53-0.83], P<.001). A smaller mean defect was associated with an increased likelihood of perceiving the blue arcs (OR=1.79 [95% CI: 1.40-2.28]); P<.001), while larger pattern standard deviation (OR=0.72 [95% CI: 0.57-0.91]; P=.005) and abnormal glaucoma hemifield test (OR=0.25 [0.10-0.65]; P=.006) were associated with a reduced likelihood of perceiving them. Older age and media opacity were also associated with an inability to perceive the blue arcs.</p><p><strong>Conclusion: </strong>In this study, the inability to perceive the blue arcs correlated with structural and functional features associated with glaucoma, although older age and media opacity were also predictors of this entoptic response.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":" ","pages":"46-55"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797830/pdf/1545-6110_v111_p046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40272746","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":"Focal venous hypertension as a pathophysiologic mechanism for tissue hypertrophy, port-wine stains, the Sturge-Weber syndrome, and related disorders: proof of concept with novel hypothesis for underlying etiological cause (an American Ophthalmological Society thesis).","authors":"Cameron F Parsa","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To provide an in-depth re-examination of assumed causes of tissue hypertrophy, port-wine stains, and the Sturge-Weber, Cobb, Klippel-Trénaunay, and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses; to provide proof of concept with new patient data; to propose a novel etiological hypothesis for the venous dysplasia in these syndromes and find supportive evidence.</p><p><strong>Methods: </strong>Data from 20 patients with port-wine stains and corneal pachymetry readings was collected prospectively by the author in an institutional referral-based practice. The literature was searched using MEDLINE, and articles and textbooks were obtained from the bibliographies of these publications.</p><p><strong>Results: </strong>Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge-Weber syndrome or isolated port-wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion.</p><p><strong>Conclusions: </strong>Contrary to traditional understanding, signs and symptoms in the Sturge-Weber and related syndromes, including both congenital and acquired port-wine stains, are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions, as in the Parkes Weber syndrome. A novel underlying etiology-prenatal venous thrombo-occlusion-is proposed to be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic tissue hypertrophy in these syndromes clarifies physiologic mechanisms for exercise-induced muscle hypertrophy to occur via venous compression and increased capillary transudation.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":" ","pages":"180-215"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871829/pdf/1545-6110_v111_p180.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31995553","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":"Is carotid ultrasound necessary in the clinical evaluation of the asymptomatic Hollenhorst plaque? (An American Ophthalmological Society thesis).","authors":"Sophie J Bakri,&nbsp;Ashraf Luqman,&nbsp;Bhupesh Pathik,&nbsp;Krishnaswamy Chandrasekaran","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the utility of carotid ultrasound in patients with asymptomatic Hollenhorst plaques.</p><p><strong>Methods: </strong>Retrospective chart review of 237 patients diagnosed with Hollenhorst plaques between 1996 and 2004. The baseline cardiovascular risk profile, medications, and carotid ultrasound findings were documented. Retinal ischemia, myocardial ischemia, and cerebrovascular events during follow-up were noted.</p><p><strong>Results: </strong>There was no statistically significant difference in the proportion of patients with carotid stenosis >40% between symptomatic (n=60) and asymptomatic (n=177) patients (32.7% vs 22.7%; P=.192, one-way ANOVA). However, symptomatic patients were statistically more likely to have stenosis >69% (25% compared with 9.2% in the asymptomatic group; P=.008, one-way ANOVA). Among asymptomatic patients, those with carotid bruit (27.1%) were more likely to have moderate carotid stenosis >40% (55.6% vs 18.6% in patients without bruit; P=.0008, one-way ANOVA) and significant stenosis >69% (37% vs 4.3% in patients without bruit; P=.0001, one-way ANOVA). Follow-up data was obtained from 32 symptomatic patients (39.6 ± 22.9 months) and 100 asymptomatic patients (41.3 ± 21.8 months). Vascular and neurologic event rates were similar between the two groups.</p><p><strong>Conclusions: </strong>Hollenhorst plaques are a marker of significant carotid disease irrespective of retinal symptoms. Carotid auscultation remains important in the examination of patients with Hollenhorst plaques and increases the yield of asymptomatic patients diagnosed with carotid stenosis. The presence of visual symptoms on presentation did not correlate with an increased risk of death or stroke compared to asymptomatic patients during follow-up. Therefore all patients with asymptomatic plaques should have a medical workup, including carotid ultrasonography.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":" ","pages":"17-23"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783250/pdf/1545-6110_v111_p017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31764025","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":"Cost-effectiveness of bevacizumab and ranibizumab for newly diagnosed neovascular macular degeneration (an American Ophthalmological Society thesis).","authors":"Joshua D Stein,&nbsp;Paula Anne Newman-Casey,&nbsp;Tavag Mrinalini,&nbsp;Paul P Lee,&nbsp;David W Hutton","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections.</p><p><strong>Methods: </strong>Using a Markov model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), the Medicare Fee Schedules, and the medical literature.</p><p><strong>Results: </strong>Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242,357 per quality-adjusted life year (QALY). Monthly ranibizumab gains an additional 0.02 QALYs vs monthly bevacizumab at an incremental cost-effectiveness ratio of more than $10 million per QALY. As-needed ranibizumab was dominated by monthly bevacizumab. In sensitivity analyses assuming a willingness to pay of $100,000 per QALY, the annual risk of serious vascular events would have to be at least 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100,000 per QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by one category (eg, from 20/25-20/40 to 20/50-20/80) after 2 years but all patients receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97,340 per QALY.</p><p><strong>Conclusion: </strong>Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":" ","pages":"56-69"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797829/pdf/1545-6110_v111_p056.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40272747","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":"Establishment of a human conjunctival epithelial cell line lacking the functional TACSTD2 gene (an American Ophthalmological Society thesis).","authors":"Shigeru Kinoshita,&nbsp;Satoshi Kawasaki,&nbsp;Koji Kitazawa,&nbsp;Katsuhiko Shinomiya","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To report the establishment of a human conjunctival epithelial cell line lacking the functional tumor-associated calcium signal transducer 2 (TACSTD2) gene to be used as an in vitro model of gelatinous drop-like corneal dystrophy (GDLD), a rare disease in which the corneal epithelial barrier function is significantly compromized by the loss of function mutation of the TACSTD2 gene.</p><p><strong>Methods: </strong>A small piece of conjunctival tissue was obtained from a GDLD patient. The conjunctival epithelial cells were enzymatically separated and dissociated from the tissue and immortalized by the lentiviral introduction of the SV40 large T antigen and human telomerase reverse transcriptase (hTERT) genes. Population doubling, protein expression, and transepithelial resistance (TER) analyses were performed to assess the appropriateness of the established cell line as an in vitro model for GDLD.</p><p><strong>Results: </strong>The life span of the established cell line was found to be significantly elongated compared to nontransfected conjunctival epithelial cells. The SV40 large T antigen and hTERT genes were stably expressed in the established cell line. The protein expression level of the tight junction-related proteins was significantly low compared to the immortalized normal conjunctival epithelial cell line. TER of the established cell line was found to be significantly low compared to the immortalized normal conjunctival epithelial cell line.</p><p><strong>Conclusions: </strong>Our conjunctival epithelial cell line was successfully immortalized and well mimicked several features of GDLD corneas. This cell line may be useful for the elucidation of the pathogenesis of GDLD and for the development of novel treatments for GDLD.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":"110 ","pages":"166-77"},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671362/pdf/1545-6110_v110_p166.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31550183","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 and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).","authors":"Christophe Baudouin,&nbsp;Alexandre Denoyer,&nbsp;Nicolas Desbenoit,&nbsp;Gregory Hamm,&nbsp;Alice Grise","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration.</p><p><strong>Methods: </strong>Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes.</p><p><strong>Results: </strong>Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations.</p><p><strong>Conclusion: </strong>BAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.</p>","PeriodicalId":23166,"journal":{"name":"Transactions of the American Ophthalmological Society","volume":"110 ","pages":"40-63"},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671366/pdf/1545-6110_v110_p040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31548691","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}