2020

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Maleki A, Ueberroth JA, Manhapra A, Walsh M, Asgari S, Chang PY, Anesi SD, Foster SC. Fixed-Luminance and Multi-Luminance Flicker Electroretinography Parameters in Patients with Early Active Birdshot Chorioretinopathy. Ocul Immunol Inflamm 2020;:1-7.Abstract
Purpose To evaluate the parameters of the Fixed-Luminance and Multi-Luminance flicker electroretinography protocol among patients with early active birdshot chorioretinopathy. Methods Fixed-Luminance magnitude, Fixed-Luminance phase, Multi-Luminance magnitude area under the curve, and Multi-Luminance phase area under the curve parameters were compared between early active birdshot chorioretinopathy patients and an age-matched control group. Results There was no statistically significant difference between the Fixed-Luminance flicker magnitude ( = .6), the Fixed-Luminance flicker phase ( = .9), and the Multi-Luminance flicker phase area under the curve ( = .55) when each was compared to the normal population; however, the difference between the mean Multi-Luminance flicker magnitude area under the curve in our patients and the healthy control group was statistically significant. ( = .003) Conclusions Multi-Luminance flicker magnitude area under the curve has been shown to be significantly different from the normal population in the early active course of the disease. Abbreviations BSCR: birdshot chorioretinopathy; cd: Cadmium; ERG: Electroretinography; FA: Fluorescein angiography; FL-: Fixed-luminance; HVF: Humphrey visual field; Hz: Hertz; ICG: Indocyanine green; m: Square meter; ML-: Multi-luminance; ms: millisecond; SITA: Swedish interactive thresholding algorithm; SWAP: Short wave-length automated perimetry.
Maleki A, Ueberroth JA, Walsh M, Foster F, Chang PY, Anesi SD, Foster CS. Combination of Intravenous Methotrexate and Methylprednisolone Therapy in the Treatment of Severe Ocular Inflammatory Diseases. Ocul Immunol Inflamm 2020;:1-5.Abstract
: To evaluate the efficacy of intravenous methotrexate and methylprednisolone in severe, sight-threatening ocular inflammatory conditions.: This was a retrospective observational case series. Patients who had received intravenous methotrexate for ocular inflammation with at least 24 months of follow-up were included in the study.: Ten patients (20 eyes) were included in this study. Mean age of the patients was 47.2 ± 17.7 (range:19-74). At 1-month follow-up visit, nine patients showed improvement and one patient failed treatment. At 12-month follow-up visit, all patients were in remission. Two patients were only on intravenous methotrexate infusions. At twenty-four-month follow-up visit, only one patient, in remission, was on intravenous methotrexate therapy. Leukopenia was the only adverse effect observed.: Intravenous methotrexate and methylprednisolone infusions can be an effective method of treatment in patients with severe, sight-threatening ocular inflammatory conditions.
Maleki A, Gomez S, Asgari S, Bosenberg Z, Manhapra A, Walsh M, Weng A, Tseng C, He C, Anesi SD, Foster SC. Diagnostic and Prognostic Roles of Serum Interleukin-6 Levels in Patients with Uveitis. Ocul Immunol Inflamm 2020;:1-6.Abstract
PURPOSE: To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis. METHODS: This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels. RESULTS: Mean IL-6 level was 1.77 ± 0.97 pg/ml and 10.2 ± 9.7 pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant ( = .015, = .000, = .03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR = 10.83, < .001), Age (OR = 0.95, = .03) and number of flare-ups (OR = 2.9, = .02). CONCLUSION: Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.
Marmamula S, Barrenkala NR, Challa R, Kumbham TR, Modepalli SB, Yellapragada R, Bhakki M, Friedman DS, Khanna RC. Falls and visual impairment among elderly residents in 'homes for the aged' in India. Sci Rep 2020;10(1):13389.Abstract
We evaluated the prevalence of falls and their association with visual impairment (VI) in elderly residents in 'homes for the aged' in Hyderabad, India. Participants aged ≥ 60 years were recruited from 41 homes, and a comprehensive eye examination was conducted. Interviews were conducted to collect personal and demographic information, systemic health status, fear of falling, depression, and history of falls in the last year. VI categories included low vision (presenting visual acuity worse than 6/18 to 3/60) and blindness (presenting visual acuity worse than 3/60). The data of 1,074 participants were analysed. The mean age was 74.4 years (standard deviation:8.7 years); 63.9% were women, 19.4% had no formal education, 28.1% were diabetic and 56.9% were hypertensive. The annual prevalence of falls was 29.1% (95% CI: 26.4-32.0). Multivariable analysis showed those with VI had significantly higher odds of falls (Odds Ratio:1.47; p = 0.043). The prevalence of falls was higher among those with VI due to uncorrected refractive errors. We found a very high prevalence of falls in elderly individuals living in 'homes for the aged' in Hyderabad, India. Addressing VI can result in fewer falls and contribute to healthy aging in India.
Marmamula S, Mitchell W, Zebardast N, Locascio J, Barrenkala NR, Kumbham TR, Modepalli SB, Khanna RC, Friedman DS. Impact of Vision Loss on Visual Function Among Elderly Residents in the "Home for the Aged" in India: The Hyderabad Ocular Morbidity in Elderly Study. Transl Vis Sci Technol 2020;9(13):11.Abstract
Purpose: The purpose of this study was to report the association between visual impairment (VI) and self-reported visual difficulty among the elderly in residential care using the Indian Vision Functioning Questionnaire (IND-VFQ-33) psychometrically validated questionnaire. Methods: Participants aged ≥ 60 years were recruited from 41 homes in Hyderabad in South India. All participants underwent detailed eye examination and interviews. Self-reported visual function was assessed using the IND-VFQ-33 questionnaire. Factor Analysis and Item Response Theory (IRT) models were used for analysis. Multivariable regression models were used to investigate associations between derived global difficulty scores versus severity and causes of VI. Presenting visual acuity worse than 6/18 in the better eye was considered as VI. Results: In total, 867 elderly participants completed the INDVFQ-33. Two latent traits ("daily activities" and "visual symptoms") were identified on factor analysis, each with uniquely loading questions. Participants with VI reported significantly higher daily activities difficulty (6 points higher) and visual symptoms difficulty (1.7 points higher) than those without VI ( < 0.05). Those with cataract reported the highest daily activities and visual symptoms difficulty (7.6 points and 2.2 points higher, respectively, < 0.05). Greater severity of VI was associated with increased self-reported difficulty for both factors, and for all causes of VI. Conclusions: We present a psychometrically validated visual questionnaire particularly suited to older adults in residential homes. We show a significant association between cause/severity of VI and difficulty with daily activities and visual symptoms after adjusting for sociodemographic and medical factors. Translational Relevance: Understanding the impact of vision loss on visual functions in the elderly will help in planning and resource allocation for developing early intervention programs for the elderly.
Marmamula S, Barrenkala NR, Challa R, Kumbam TR, Modepalli SB, Yellapragada R, Bhakki M, Khanna RC, Friedman DS. Uncorrected refractive errors for distance among the residents in 'homes for the aged' in South India-The Hyderabad Ocular Morbidity in Elderly Study (HOMES). Ophthalmic Physiol Opt 2020;40(3):343-349.Abstract
PURPOSE: To investigate the prevalence and risk factors of Uncorrected Refractive Errors (URE) for distance in elderly residents in 'homes for the aged' in Hyderabad, India. METHODS: Individuals aged ≥60 years and residing in 'homes for the aged' in Hyderabad, India for a minimum of 1 month and providing consent for participation were recruited. All participants underwent visual acuity assessment, refraction, slit lamp biomicroscopy, intraocular pressure measurement, fundus examination, and retinal imaging. Monocular presenting visual acuity was recorded using a logMAR chart. Objective and subjective refraction were performed, and best-corrected visual acuity was recorded. URE was defined as presenting visual acuity worse than 6/12 but improving to 6/12 or better with refraction. Univariable and multivariable logistic regression analyses were used to assess the risk factors associated with URE. RESULTS: In total, 1 513 elderly participants were enumerated from 41 homes of which 1 182 participants (78.1%) were examined. The mean age of participants was 75.0 years (standard deviation 8.8 years; range: 60-108 years). 35.4% of those examined were men and 20.3% had no formal education. The prevalence of URE was 13.5% (95% CI: 11.5-15.5; n = 159). On applying multiple logistic regression analysis, compared to those living in private homes, the odds of URE were significantly higher among the elderly living in the aided homes (OR: 1.65; 95% CI: 1.11-2.43) and free homes (OR: 1.67; 95% CI: 1.00-2.80). As compared to those who reported having an eye examination in the last 3 years, the odds of URE were higher among those who never had an eye examination in the last three years (OR: 1.51; 95% CI: 1.07-2.14). Similarly, those who had unilateral cataract surgery (OR: 1.80; 95% CI: 1.10-2.93) or bilateral cataract surgery (1.69; 95% CI: 1.10-2.56) had higher odds of URE compared to those elderly who were not operated for cataract. Gender, self-report of diabetes, and education were not associated with URE. CONCLUSIONS: A large burden of URE was found among the residents in the 'homes for the aged' in Hyderabad, India which could be addressed with a pair of glasses. Over 40% of the residents never had an eye examination in the last three years, which indicates poor utilisation of eye care services by the elderly. Regular eye examinations and provision of spectacles are needed to address needless URE for distance among the elderly in residential care in India.
Marques JP, Pires J, Simão J, Marques M, Gil JQ, Laíns I, Alves D, Nunes S, Cachulo ML, Miller JB, Vavvas DG, Miller JW, Husain D, Silva R. Validation of RetmarkerAMD as a semiautomatic grading software for AMD. Eye (Lond) 2020;34(3):600-602.
Martinez-Carrasco R, Argüeso P, Fini EM. Dynasore protects ocular surface mucosal epithelia subjected to oxidative stress by maintaining UPR and calcium homeostasis. Free Radic Biol Med 2020;160:57-66.Abstract
The mucosal epithelia of the ocular surface protect against external threats to the eye. Using a model of human stratified corneal epithelial cells with mucosal differentiation, we previously demonstrated that a small molecule inhibitor of dynamin GTPases, dynasore, prevents damage to cells and their transcellular barriers when subjected to oxidative stress. Investigating mechanisms, we now report the novel finding that dynasore acts by maintaining Ca homeostasis, thereby inhibiting the PERK branch of the unfolded protein response (UPR) that promotes cell death. Dynasore was found to protect mitochondria by preventing mitochondrial permeability transition pore opening (mPTP), but, unlike reports using other systems, this was not mediated by dynamin family member DRP1. Necrostatin-1, an inhibitor of RIPK1 and lytic forms of programmed cell death, also inhibited mPTP opening and further protected the plasma membrane barrier. Significantly, necrostatin-1 did not protect the mucosal barrier. Oxidative stress increased mRNA for sXBP1, a marker of the IRE1 branch of the UPR, and CHOP, a marker of the PERK branch. It also stimulated phosphorylation of eIF2α, the upstream regulator of CHOP, as well as an increase in intracellular Ca. Dynasore selectively inhibited the increase in PERK branch markers, and also prevented the increase intracellular Ca in response to oxidative stress. The increase in PERK branch markers were also inhibited when cells were treated with the cell permeable Ca chelator, BAPTA-AM. To our knowledge, this is the first time that dynasore has been shown to have an effect on the UPR and suggests therapeutic applications.
Mayro EL, Wang M, Elze T, Pasquale LR. The impact of artificial intelligence in the diagnosis and management of glaucoma. Eye (Lond) 2020;34(1):1-11.Abstract
Deep learning (DL) is a subset of artificial intelligence (AI), which uses multilayer neural networks modelled after the mammalian visual cortex capable of synthesizing images in ways that will transform the field of glaucoma. Autonomous DL algorithms are capable of maximizing information embedded in digital fundus photographs and ocular coherence tomographs to outperform ophthalmologists in disease detection. Other unsupervised algorithms such as principal component analysis (axis learning) and archetypal analysis (corner learning) facilitate visual field interpretation and show great promise to detect functional glaucoma progression and differentiate it from non-glaucomatous changes when compared with conventional software packages. Forecasting tools such as the Kalman filter may revolutionize glaucoma management by accounting for a host of factors to set target intraocular pressure goals that preserve vision. Activation maps generated from DL algorithms that process glaucoma data have the potential to efficiently direct our attention to critical data elements embedded in high throughput data and enhance our understanding of the glaucomatous process. It is hoped that AI will realize more accurate assessment of the copious data encountered in glaucoma management, improving our understanding of the disease, preserving vision, and serving to enhance the deep bonds that patients develop with their treating physicians.
McColgan NM, Feeley MN, Woodward AM, Guindolet D, Argüeso P. The O-GlcNAc modification promotes terminal differentiation of human corneal epithelial cells. Glycobiology 2020;30(11):872-880.Abstract
Dynamic modification of nuclear and cytoplasmic proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) plays an important role in orchestrating the transcriptional activity of eukaryotic cells. Here, we report that the O-GlcNAc modification contributes to maintaining ocular surface epithelial homeostasis by promoting mucin biosynthesis and barrier function. We found that induction of human corneal epithelial cell differentiation stimulated the global transfer of O-GlcNAc to both nuclear and cytosolic proteins. Inflammatory conditions, on the other hand, were associated with a reduction in the expression of O-GlcNAc transferase at the ocular surface epithelia. Loss- and gain-of-function studies using small interfering RNA targeting O-GlcNAc transferase, or Thiamet G, a selective inhibitor of O-GlcNAc hydrolase, respectively, revealed that the presence of O-GlcNAc was necessary to promote glycocalyx barrier function. Moreover, we found that Thiamet G triggered a correlative increase in both surface expression of MUC16 and apical epithelial cell area while reducing paracellular permeability. Collectively, these results identify intracellular protein O-glycosylation as a novel pathway responsible for promoting the terminal differentiation of human corneal epithelial cells.
McKay TB, Schlötzer-Schrehardt U, Pal-Ghosh S, Stepp MA. Integrin: Basement membrane adhesion by corneal epithelial and endothelial cells. Exp Eye Res 2020;:108138.Abstract
Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells, the extracellular matrix, and gene expression in the nucleus. Changes in integrin expression in corneal epithelial cells and corneal endothelial cells impacts their adhesion to the epithelial basement membrane (EpBM) and Descemet's membrane, respectively. Integrins also play roles in assembly of basement membranes by both activating TGFβ1 and other growth factors. Over the past two decades, this knowledge has been translated into methods to grow corneal epithelial and endothelial cells in vitro for transplantation in the clinic thereby transforming clinical practice and quality of life for patients. Current knowledge on the expression and function of the integrins that mediate adhesion to the basement membrane expressed by corneal epithelial and endothelial cells in health and disease is summarized. This is the first review to discuss similarities and differences in the integrins expressed by both cell types.
McKay MK, Borkar DS, Sevgi DD, Susarla G, Papaliodis GN, Sobrin L. Comparison of Modified Posterior Sub-Tenon's vs. Trans-Septal Triamcinolone Injection for Non-infectious Uveitis. Ocul Immunol Inflamm 2020;:1-8.Abstract
: To compare the safety and efficacy of trans-septal vs. modified posterior sub-Tenon's (PST) corticosteroid injections for noninfectious uveitis.: Retrospective comparison of periocular triamcinolone injection by modified PST (n = 36) vs. traditional trans-septal (n = 79) techniques. Safety and efficacy outcomes were analyzed with regression models.: There was no significant difference in visual acuity improvement between the groups at 6 months. There were higher rates of vitritis resolution in the modified PST group but this was not statistically significant (85.7% vs 62.9%, = .07). Intraocular pressure (IOP) elevation rate trended higher with the modified PST injection (21.9% vs 9.0%, = .06), with no instances of glaucoma surgery in either group. Two modified PST injection patients with refractory IOP rises had IOP normalization after corticosteroid depot removal. One year cataract surgery rates were similar.: Modified PST injection offers clinical efficacy but with possibly higher IOP response rate which could be managed with corticosteroid removal.
McKay TB, Serjersen H, Hjortdal J, Zieske JD, Karamichos D. Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients. Sci Rep 2020;10(1):9426.Abstract
Keratoconus (KC) is classically considered a non-inflammatory condition caused by central corneal thinning that leads to astigmatism and reduced visual acuity. Previous studies have identified increased systemic levels of pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9, suggesting that KC may have an inflammatory component in at least a subset of patients. In this study, we evaluated the levels of different immunoglobulins (light and heavy chains) based on Ig α, Ig λ, Ig κ, Ig µ, and Ig heavy chain subunits in non-KC tears (n = 7 control individuals) and KC tears (n = 7 KC patients) using tandem-liquid chromatography mass spectrometry. The most abundant Ig heavy chains detected in both control individuals and KC patients were Ig α-1 and Ig α-2 likely correlating to the higher IgA levels reported in human tears. We identified significant differences in immunoglobulin κ-chain V-II levels in KC patients compared to control individuals with no significant difference in Ig κ/Ig λ ratios or heavy chain levels. Our study supports previous findings suggesting that KC possesses a systemic component that may contribute to the KC pathology. Further studies are required to define causality and establish a role for systemic immune system-dependent factors and pro-inflammatory processes in KC development or progression.
McKay TB, Guo X, Hutcheon AEK, Karamichos D, Ciolino JB. Methods for Investigating Corneal Cell Interactions and Extracellular Vesicles In Vitro. Curr Protoc Cell Biol 2020;89(1):e114.Abstract
Science and medicine have become increasingly "human-centric" over the years. A growing shift away from the use of animals in basic research has led to the development of sophisticated in vitro models of various tissues utilizing human-derived cells to study physiology and disease. The human cornea has likewise been modeled in vitro using primary cells derived from corneas obtained from cadavers or post-transplantation. By utilizing a cell's intrinsic ability to maintain its tissue phenotype in a pre-designed microenvironment containing the required growth factors, physiological temperature, and humidity, tissue-engineered corneas can be grown and maintained in culture for relatively long periods of time on the scale of weeks to months. Due to its transparency and avascularity, the cornea is an optimal tissue for studies of extracellular matrix and cell-cell interactions, toxicology and permeability of drugs, and underlying mechanisms of scarring and tissue regeneration. This paper describes methods for the cultivation of corneal keratocytes, fibroblasts, epithelial, and endothelial cells for in vitro applications. We also provide detailed, step-by-step protocols for assembling and culturing 3D constructs of the corneal stroma, epithelial- and endothelial-stromal co-cultures and isolation of extracellular vesicles. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Isolating and culturing human corneal keratocytes and fibroblasts Basic Protocol 2: Isolating and culturing human corneal epithelial cells Basic Protocol 3: Isolating and culturing human corneal endothelial cells Basic Protocol 4: 3D corneal stromal construct assembly Basic Protocol 5: 3D corneal epithelial-stromal construct assembly Basic Protocol 6: 3D corneal endothelial-stromal construct assembly Basic Protocol 7: Isolating extracellular vesicles from corneal cell conditioned medium Support Protocol: Cryopreserving human corneal fibroblasts, corneal epithelial cells, and corneal endothelial cells.
McKay TB, Hutcheon AEK, Guo X, Zieske JD, Karamichos D. Modeling the cornea in 3-dimensions: Current and future perspectives. Exp Eye Res 2020;197:108127.Abstract
The cornea is an avascular, transparent ocular tissue that serves as a refractive and protective structure for the eye. Over 90% of the cornea is composed of a collagenous-rich extracellular matrix within the stroma with the other 10% composed by the corneal epithelium and endothelium layers and their corresponding supporting collagen layers (e.g., Bowman's and Descemet's membranes) at the anterior and posterior cornea, respectively. Due to its prominent role in corneal structure, tissue engineering approaches to model the human cornea in vitro have focused heavily on the cellular and functional properties of the corneal stroma. In this review, we discuss model development in the context of culture dimensionality (e.g., 2-dimensional versus 3-dimensional) and expand on the optical, biomechanical, and cellular functions promoted by the culture microenvironment. We describe current methods to model the human cornea with focus on organotypic approaches, compressed collagen, bioprinting, and self-assembled stromal models. We also expand on co-culture applications with the inclusion of relevant corneal cell types, such as epithelial, stromal keratocyte or fibroblast, endothelial, and neuronal cells. Further advancements in corneal tissue model development will markedly improve our current understanding of corneal wound healing and regeneration.
McKay TB, Hutcheon AEK, Zieske JD. Biology of corneal fibrosis: soluble mediators, integrins, and extracellular vesicles. Eye (Lond) 2020;34(2):271-278.Abstract
Corneal fibrosis develops in response to injury, infection, postsurgical complications, or underlying systemic disease that disrupts the homeostasis of the tissue leading to irregular extracellular matrix deposition within the stroma. The mechanisms that regulate corneal scarring are focused heavily on the canonical transforming growth factor-β pathway and relevant activators, and their role in promoting myofibroblast differentiation. In this paper, we discuss the biochemical pathways involved in corneal fibrosis in the context of different injury models-epithelial debridement, superficial keratectomy, and penetrating incision. We elaborate on the interplay of the major pro-fibrotic factors involved in corneal scar development (e.g., transforming growth factor-β1, thrombospondin-1, and ανβ6), and explore a novel role for extracellular vesicles secreted by the wounded epithelium and the importance of the basement membrane.
Mehta MC, Narayanan R, Thomas Aretz H, Khanna R, Rao GN. The L V Prasad Eye Institute: A comprehensive case study of excellent and equitable eye care. Healthc (Amst) 2020;:100408.Abstract
Global healthcare delivery systems are facing ever-increasing challenges on multiple fronts. The need to study and define successful models of care delivery systems has become increasingly important. The L V Prasad Eye Institute (LVPEI) has a distinctive eye care delivery system offering rich lessons at many operational levels. The system has been developed on the basis of LVPEI's foundational public eye health study, and follows a complexity-driven (dependent on disease complexity) clinical care system forming a five-tier pyramidal model - at the apex is the quaternary care centre at Hyderabad, followed by increasing numbers of tertiary, secondary or community, primary, and rural eye care centres, where the revenue from paying patients covers free-care via an economic cross-subsidy. This has achieved a level of scale, efficiency, social impact, and clinical and scientific innovation rarely seen in a single health system. Building on the foundational principles of this pyramidal care with a robust economic cross-subsidy model, LVPEI has seamlessly established successful professional, academic, and educational systems that combine innovation, scientific discovery, and the development of in-house technologies focused on improving service quality and clinical decision making. In this case study, we show that all elements of the LVPEI model are practical and may be applicable to academic medical centres in diverse healthcare settings; currently, this is being tested in Liberia, West Africa.
Mihailovic A, Varadaraj V, Ramulu PY, Friedman DS. Evaluating Goldmann Applanation Tonometry Intraocular Pressure Measurement Agreement Between Ophthalmic Technicians and Physicians. Am J Ophthalmol 2020;219:170-176.Abstract
PURPOSE: To examine IOP measurement disagreement between technicians and physicians and the impact of an educational intervention on the short and long-term disagreement in IOP measurement using Goldmann applanation tonometry. DESIGN: Prospective study designed to enhance measurement reliability. SETTING: A glaucoma clinic at a university hospital. StudyPopulation: 6 technicians and 2 physicians. INTERVENTION: An educational intervention was implemented for the technicians to improve IOP measurement agreement with physicians. MainOutcomeMeasures: Frequency of IOP measurement disagreement between physicians and technicians, defined as a difference in IOP of >2 or >3 mm Hg and assessed at baseline and immediately and 6 months postintervention. RESULTS: IOP was evaluated for a total of 529 eyes (physician measured mean IOP = 16.4 mm Hg [SD = 5.9]), 30 per technician-physician pair for each data collection period: baseline, immediately postintervention and 6 months postintervention. At baseline, physicians disagreed 17% and 7% of the time when measuring IOP using >2 and >3 mm Hg to define disagreement, respectively, whereas the average disagreement between technicians and physicians was 25% and 13%. Disagreement was greater at IOPs greater than 20 mm Hg. No significant changes were noted in the frequency of disagreement between technicians and physicians immediately or 6 months postintervention. CONCLUSIONS: Two physicians measuring the same patient in the same room disagreed by >2 mm Hg in 17% of patients' eyes, and this amount of disagreement was even higher when comparing physicians to certified technicians. An educational intervention did not improve agreement in IOP measurements between technicians and physicians. This highlights an important limitation of Goldmann tonometry.
Milman T, Jakobiec FA, Lally SE, Shields JA, Shields CL, Eagle RC. Lacrimal Gland Hamartoma (Formerly Termed Dacryoadenoma). Am J Ophthalmol 2020;217:189-197.Abstract
PURPOSE: Since the original description of "dacryadenoma" by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion. DESIGN: Retrospective observational case series. METHODS: Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded. RESULTS: Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75%), or nasal (1/4, 25%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75%) or associated with foreign body sensation (1/4, 25%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50%) or rare (2/2, 50%) ducts and rare acinar zymogen granules (3/4, 75%). CONCLUSION: Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.
Minaeva O, Sarangi S, Ledoux DM, Moncaster JA, Parsons DS, Washicosky KJ, Black CA, Weng FJ, Ericsson M, Moir RD, Tripodis Y, Clark JI, Tanzi RE, Hunter DG, Goldstein LE. In Vivo Quasi-Elastic Light Scattering Eye Scanner Detects Molecular Aging in Humans. J Gerontol A Biol Sci Med Sci 2020;75(9):e53-e62.Abstract
The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. The human lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, accumulate molecular alterations throughout life, and are optically accessible in vivo. We used quasi-elastic light scattering (QLS) to measure age-dependent signals in lenses of healthy human subjects. Age-dependent QLS signal changes detected in vivo recapitulated time-dependent changes in hydrodynamic radius, protein polydispersity, and supramolecular order of human lens proteins during long-term incubation (~1 year) and in response to sustained oxidation (~2.5 months) in vitro. Our findings demonstrate that QLS analysis of human lens proteins provides a practical technique for noninvasive assessment of molecular aging in vivo.

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