The American Journal of Ophthalmology Will Publish American Ophthalmological Society Theses.
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ABSTRACT:
SUBMITTER: Parrish RK
PROVIDER: S-EPMC8383345 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
The American Journal of Ophthalmology Will Publish American Ophthalmological Society Theses.
Parrish Richard K RK Chew Emily Y EY Grossniklaus Hans E HE
American journal of ophthalmology 20180411
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Project description:To improve understanding of dry eye disease and highlight a subgroup of patients who have a component of central sensitization and neuropathic pain contributing to their condition.Prospective, cross-sectional, IRB-approved study comparing isolated dry eye disease (n=48) to fibromyalgia (positive control; n=23) and healthy (negative control; n=26) individuals with ocular surface examination, corneal confocal microscopy, quantitative sensory testing, and self-reported ocular symptoms and systemic associations. A subset of patients also underwent skin biopsy and/or brain neuroimaging. Dry eye patients were split into concordant (ie, those with dry eyes on examination) and discordant (ie, those with dry eye symptoms but normal examination) subgroups for further analysis. We hypothesized that on the systemic measures included, concordant patients would resemble healthy controls, whereas discordant patients would show evidence of centralized mechanisms similar to fibromyalgia.Schirmer test and Ocular Surface Disease Index (OSDI) scores indicated significant decreases in tear production (Schirmer: healthy, 18.5±8.2 mm; dry, 11.2±5.4 mm; fibromyalgia, 14.4±7.5; P<.001) and increases in self-reported dry eye symptoms (OSDI: healthy, 1.9±3.0; dry, 20.3±17.7; fibromyalgia, 20.3±17.1; P<.001) in the dry eye and fibromyalgia patients, compared to controls. The discordant subgroup had decreased corneal nerve density and decreased visual quality-of-life scores, similar to patients with fibromyalgia. Concordant patients were more similar to healthy controls on these measures.Individuals with discordant dry eye may have a central pathophysiologic mechanism leading to their eye pain symptoms, which could be an important factor to consider in treatment of chronic idiopathic dry eye.
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Project description:PurposeTo develop a new diabetic retinopathy severity scoring system and to determine if it can monitor changes from baseline as well as identify precise features that have changed over time. Such a grading system could potentially provide an understanding of the impact of treatments utilizing an algorithmic scoring technique.MethodsThe traditional ETDRS grading system was examined and a flow algorithm based on the grading approach was created. All visual comparative assessment points, relying on identification of features in relation to prior standard photographic images, were evaluated and quantified. A new grading form was created that provided fields that captured all relevant features required for determining the ETDRS grading score. A computer software algorithm was developed that examines all entered fields and calculates the appropriate diabetic severity score.ResultsThis diabetic retinopathy scoring algorithm system was successful in generating a severity score comparable to traditional methods of grading images. Validation with traditionally graded images was performed, demonstrating that in a majority of cases, the severity scores were comparable. The algorithmic grading system was then used to analyze images obtained in a large clinical study of diabetic macular edema, resulting in data regarding baseline scoring values, as well as detailed features of the microvasculature that drove the severity scoring results, and changes seen during the trial.ConclusionThis new algorithmic diabetic severity scoring system provides a means to monitor the progression or regression of retinopathy with therapeutic intervention as well as assess the individual microvascular features that may be modified over the course of treatment.
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Project description:PurposeMutations of keratoepithelin (KE) and myocilin (MYOC) have been linked to certain types of inherited corneal stromal dystrophy and open-angle glaucoma, respectively. In this study, the feasibility of using small interfering RNAs (siRNAs) to suppress the expression of keratoepithelin and myocilin and their capabilities to reduce the related cytotoxic effects caused by mutant myocilins were investigated.MethodscDNAs of human KE gene and myocilin gene were amplified by polymerase chain reaction and subcloned into pEGFP-N1 to construct respective plasmids, KEpEGFP and MYOCpEGFP, to produce fluorescence-generating fusion proteins. Short hairpin RNAs (shRNAs) were generated from an RNA polymerase III promoter-driven vector (pH1-RNA). Transformed HEK293 and trabecular meshwork (TM) cells were cotransfected via liposomes with either KEpEGFP or MYOCpEGFP and respective shRNA-generating plasmids to evaluate the suppression efficacy of shRNAs. Suppression of KE-EGFP by KE-specific shRNAs was evaluated by fluorescence microscopy and Western blotting. Suppression of MYOC-EGFP by myocilin-specific shRNAs was quantified with UN-SCAN-IT software on digitized protein bands of Western blots. A BiP promoter-driven luciferase reporter assay was used to evaluate the stress response of TM cells induced by misfolded mutant myocilins.ResultsTwo KE-specific shRNAs that effectively suppressed the expression of KE-EGFP in HEK293 cells were identified. One shRNA (targeting the coding sequence starting at 1528bp of KE) reduced the expression of KE-EGFP approximately by 50%, whereas the other shRNA (targeting the 3'-UTR region of KE) suppressed greater than 80% of the expression. Cotransfection of MYOCpEGFP and various shRNA-generating plasmids targeting different regions of myocilin (containing amino acid residues R76, E352, K423, or N480 associated with inherited glaucoma) showed effective reduction of MYOC-EGFP, ranging from 78% to 90% on average. The activation of BiP gene (as a stress response induced by mutant myocilins) in transformed TM cells was significantly reduced when mutant myocilin proteins were suppressed by myocilin-specific shRNAs.ConclusionsKE- or myocilin-specific shRNAs could effectively suppress the expression of recombinant KE or myocilin proteins and the related cytotoxicity of mutant myocilins. RNA interference may have future therapeutic implications in suppressing these genes.
| S-EPMC2258103 | biostudies-literature
Project description:PurposeCYP1B1 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.MethodsTwo 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.ResultsBased 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.ConclusionsOur 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.
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Project description:ImportanceBecause women remain underrepresented in leadership positions in medicine, including ophthalmology, knowledge of sex composition of ophthalmic journal editorial and professional society boards seems warranted.ObjectivesTo investigate the sex composition of ophthalmic journal editorial and professional society boards and compare the publication productivity and number of citations of male vs female board members.Design, setting, and participantsIn this cross-sectional study, the SCImago Journal Rank indicator was used to identify the 20 highest-ranked ophthalmology journals. Faculty members from each ophthalmic subspecialty were surveyed within a US academic ophthalmology department to identify 15 influential ophthalmology societies. The 2018 board members of each journal and society were identified from the journals' and societies' official websites, and the sex of each individual was recorded. Information regarding journals and societies was collected from October 1 to December 31, 2018. The Scopus database was accessed in January 2019 and then used to find each member's h-index and m-quotient.Main outcomes and measuresThe h-index, defined as the highest number of an author's publications that received at least h number of citations, was calculated for each board member. The m-quotient, which accounts for varying lengths of academic careers, was calculated by dividing the h-index by the number of years since first publication.ResultsOf the 1077 members of ophthalmic journal editorial and society leadership boards, 797 (74.0%) were men and 280 (26.0%) were women. Among the 24 editors in chief of the 20 journals investigated, 23 (95.8%) were male. Thirteen of the 15 professional society presidents (86.7%) were men. Male board members had significantly higher median h-indexes (male vs female journals: 34 [interquartile range {IQR}, 23-47] vs 28 [IQR, 19-40], P < .001; male vs female societies: 27 [IQR, 15-41] vs 17 [IQR, 8-32], P = .006), median publication numbers (male vs female journal board members: 157 [IQR, 88-254] vs 109 [IQR, 66-188], P < .001; male vs female society board members: 109 [IQR, 57-190] vs 58 [IQR, 28-139, P = .001), and median citations (male vs female journal board members: 4027 [IQR, 1897-8005] vs 2871 [IQR, 1344-5852], P < .001; male vs female society board members: 2228 [IQR, 1005-5069] vs 1090 [IQR, 410-2527], P = .003). However, the median m-quotients for male and female board members were comparable (male vs female journal board members: 1.2 [IQR, 0.8-1.6] vs 1.1 [IQR, 0.8-1.5], P = .54; male vs female society board members: 1.0 [IQR, 0.7-1.4] vs 0.9 [IQR, 0.6-1.3], P = .32).Conclusions and relevanceThe findings suggest that the sex composition on journal editorial and professional society boards in ophthalmology is consistent with the sex composition of ophthalmologists in the US, as reported by the Association of American Colleges, but that editor in chief and society president positions are male dominated despite the apparent equality in academic productivity.
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Project description:PurposeTo assess the findings, visual morbidity, and surgical intervention in Schnyder crystalline corneal dystrophy (SCCD).MethodsRetrospective case series of 115 affected individuals from 34 SCCD families identified since 1989. Age, uncorrected visual acuity, best-corrected visual acuity (BCVA), corneal findings, and ocular surgery were recorded. Prospective phone, e-mail, or written contact provided updated information. Patients were divided into 3 age categories for statistical analysis: less than 26 years of age, 26 to 39 years of age, and 40 years of age and older.ResultsMean age on initial examination was 38.8 +/- 20.4 (range, 2-81) with follow-up of 55 of 79 (70%) of American patients. While there were no statistical significant correlations between logMAR visual acuity and age (logMAR BCVA =.033 + .002 x age; R =.21), the linear regression showed the trend of worse visual acuity with age. BCVA at > or =40 years was decreased compared to <40 (P < .0001), although mean BCVA was > 20/30 in both groups. Twenty-nine of 115 patients had corneal surgery with 5 phototherapeutic keratectomy (3 patients), and 39 penetrating keratoplasty (PKP) (27 patients). PKP was reported in 20 of 37 (54%) patients > or =50 years and 10 of 13 (77%) of patients > or =70. BCVA 1 year prior to PKP in 15 eyes (9 patients) ranged from 20/25 to 20/400 including 7 eyes with other ocular pathology. BCVA in the remaining 8 eyes was 20/25 to 20/70 with 3 of these 4 patients reporting preoperative glare. Chart and phone survey suggested increasing difficulty with photopic vision with aging.ConclusionAlthough excellent scotopic vision continues until middle age in SCCD, most patients had PKP by the 7th decade. SCCD causes progressive corneal opacification, which may result in glare and disproportionate loss of photopic vision.
| S-EPMC2258126 | biostudies-literature
Project description:PurposeThis study aims to improve the apparent motility of ocular prosthetic devices using technology. Prevailing ocular prostheses are acrylic shells with a static eye image rendered on the convex surface. A limited range of ocular prosthetic movement and lack of natural saccadic movements commonly causes the appearance of eye misalignment that may be disfiguring. Digital screens and computational systems may obviate current limitations in eye prosthetic motility and help prosthetic wearers feel less self-conscious about their appearance.MethodsWe applied convoluted neural networks (CNNs) to track pupil location in various conditions. These algorithms were coupled to a microscreen digital prosthetic eye (DPE) prototype to assess the ability of the system to capture full ocular ductions and saccadic movements in a miniaturized, portable, and wearable system.ResultsThe CNNs captured pupil location with high accuracy. Pupil location data were transmitted to a miniature screen ocular prosthetic prototype that displayed a dynamic contralateral eye image. The transmission achieved a full range of ocular ductions and with grossly undetectable latency. Lack of iris and sclera color and detail, as well as constraints in luminosity, dimensionality and image stability limited the real eye appearance. Yet, the digitally rendered eye moved in the same amplitude and velocity as the native, tracked eye.ConclusionsReal-time image processing using CNNs coupled to microcameras and a miniscreen DPE may offer improvements in amplitude and velocity of apparent prosthetic eye movement. These developments, along with ocular image precision, may offer a next-generation eye prosthesis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
| S-EPMC8502785 | biostudies-literature
Project description:PURPOSE: To use an integrated proteohistologic approach to gain insight into the anterior segment alterations in the buphthalmic rabbit. METHODS: Eyes from 2- and 5-year-old buphthalmic and normal rabbits (n=20) were studied histologically. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of aqueous humor (AH) was used to determine differential protein expression between animal groups. Western blot and immunohistochemistry were performed on selected differentially expressed proteins identified by LC-MS/MS. RESULTS: The buphthalmic rabbits manifested a mild clinical phenotype with typical angle anomalies that appeared progressive by histology. Significantly thickened Descemet's membrane (DM) and anterior lens capsule in all buphthalmic rabbits showed increased fibronectin and collagen-IV immunolabeling. LC-MS/MS applying stringent filtering criteria revealed significant differential expression of several AH proteins in these rabbits. The protein of interest in the 2-year-old group was histidine-rich glycoprotein, and those in the 5-year-old group included alpha-2-HS-glycoprotein, clusterin, apolipoprotein E, interphotoreceptor retinoid-binding protein, transthyretin, cochlin, gelsolin, haptoglobin, hemopexin, and beta-2 microglobulin. The proteomic data for selected proteins was validated by Western blot and immunohistochemistry. A wide range of functional groups were affected by the altered AH proteins. These included extracellular matrix modulation, regulation of apoptosis, oxidative stress, and protein transport. CONCLUSIONS: Multiple anterior segment alterations were histologically identified in the buphthalmic rabbits that showed progressive changes with age. The differentially expressed AH proteins in these rabbits suggest a multifunctional role for AH in modulating pathologic changes in DM, anterior lens capsule, and the angular meshwork in these animals.
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