All

Wang J, Chen D, Sullivan DA, Xie H, Li Y, Liu Y. Expression of Lubricin in the Human Amniotic Membrane. Cornea 2020;39(1):118-121.Abstract
PURPOSE: Lubricin, a boundary lubricant, is the body's unique antiadhesive, antifibrotic, antifriction, and antiinflammatory glycoprotein. This amphiphile is produced by numerous tissues and acts to regulate a number of processes, such as homeostasis, shear stress, tissue development, innate immunity, inflammation, and wound healing. We hypothesize that lubricin is also synthesized and expressed by the amniotic membrane (AM), which also possesses antiadhesive, antifibrotic, and antiinflammatory properties. We also hypothesize that lubricin, at least in part, mediates these AM capabilities. Our goal was to test our hypothesis. METHODS: We obtained multiple samples of fresh, cryopreserved (CP), and freeze-dried (FD) human AMs, as well as fresh placental tissue as positive controls, and processed them for light microscopy, immunofluorescence, and western blot analyses. We also evaluated the ability of recombinant human lubricin to associate with FD-AMs. RESULTS: Our results demonstrate that all fresh placental, fresh AM, and CP-AM samples contained lubricin. Lubricin was expressed in placental chorionic villi, AM epithelial and stromal cells, and CP-AM epithelia. No lubricin could be detected in FD-AMs but could be restored in FD-AMs after overnight incubation with recombinant human lubricin. CONCLUSIONS: This study supports our hypothesis that lubricin is expressed in human AMs. In addition, our data show that preservation methods influence the extent of this expression. Indeed, the disappearance of lubricin in FD-AMs may explain why dried AM reportedly loses its antiinflammatory and antiscarring abilities. It is possible that lubricin may mediate, at least in part, many of the biological properties of AMs.
Xiao J, Adil MY, Chen X, Utheim ØA, Ræder S, Tønseth KA, Lagali NS, Dartt DA, Utheim TP. Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity. Am J Ophthalmol 2020;209:160-167.Abstract
PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. STUDY POPULATION: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P < 0.01 and P < 0.006, respectively). CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss.
Bressler NM, Beaulieu WT, Bressler SB, Glassman AR, Melia MB, Jampol LM, Jhaveri CD, Salehi-Had H, Velez G, Sun JK, Sun JK. ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND RISK OF TRACTION RETINAL DETACHMENT IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY: Pooled Analysis of Five DRCR Retina Network Randomized Clinical Trials. Retina 2020;40(6):1021-1028.Abstract
PURPOSE: To investigate whether anti-vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR. METHODS: Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level ≥61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization. RESULTS: The 1-year cumulative probability of TRD was 6.8% (95% confidence interval: 4.6%-9.9%, 25 events) in control-group eyes and 4.8% (95% confidence interval: 3.2%-7.3%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95% confidence interval: 0.54-1.66, P = 0.86]). The cumulative probability of vitrectomy for TRD was 4.4% (16 events) in control-group eyes and 2.2% (9 events) in anti-VEGF group eyes (P = 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity. CONCLUSION: These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.
Sakurada Y, Fragiotta S, Leong BCS, Parikh R, Hussnain AS, Freund BK. RELATIONSHIP BETWEEN CHOROIDAL VASCULAR HYPERPERMEABILITY, CHORIOCAPILLARIS FLOW DENSITY, AND CHOROIDAL THICKNESS IN EYES WITH PACHYCHOROID PIGMENT EPITHELIOPATHY. Retina 2020;40(4):657-662.Abstract
PURPOSE: To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy. METHODS: Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm × 12-mm swept-source optical coherence tomography, 12-mm × 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm × 3-mm area to explore the relationship between these 2 factors. RESULTS: Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P < 0.001). The mean choriocapillaris flow density ratio was 0.86 ± 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P < 0.001, 455 ± 122 µm vs. 297 ± 93 µm). CONCLUSION: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.
Tolesa K, Abateneh A, Kempen JH, Gelaw Y. Patterns of Uveitis among Patients Attending Jimma University Department of Ophthalmology, Jimma, Ethiopia. Ocul Immunol Inflamm 2020;28(7):1109-1115.Abstract
: Uveitis is an important cause of blindness and ocular morbidity in the world. The patterns of uveitis have not been well characterized in sub-Saharan Africa. : To describe the characteristics of uveitis among patients presenting to Jimma University Department of Ophthalmology (JUDO) from July 2013 to December 2014. : This hospital-based prospective cross-sectional study included all new uveitis patients visiting JUDO outpatient department during the study period. : Among 98 patients diagnosed with uveitis, anterior uveitis was found in 74.5% of patients. Majority of the patients, 83.7%, had unilateral uveitis. A uveitis syndrome was identified in 22.5% of cases; of these 15 (68.2%) were infectious. Herpes simplex uveitis was the commonest infectious cause (53.3%) while Toxoplasmosis was the most common cause of posterior uveitis (60%). : Anterior uveitis was the most common pattern found among uveitis patients. Herpes simplex and toxoplasmic chorioretinitis were the most common-identified infectious causes.
Argüeso P. Disrupted Glycocalyx as a Source of Ocular Surface Biomarkers. Eye Contact Lens 2020;46 Suppl 2:S53-S56.Abstract
The glycocalyx is a dense and diverse coat of glycans and glycoconjugates responsible for maintaining cell surface integrity and regulating the interaction of cells with the external environment. Transmembrane mucins such as MUC1 and MUC16 comprise a major component of the epithelial glycocalyx and are currently used to monitor disease progression in cancer. At the ocular surface, multiple lines of evidence indicate that abnormal expression of the enzymes responsible for glycan biosynthesis during pathological conditions impairs the glycosylation of transmembrane mucins. It is now becoming clear that these changes contribute to modify the interaction of mucins with galectin-3, a multimeric lectin crucial for preserving the ocular surface epithelial barrier. This review highlights the potential of using the epithelial glycocalyx as a reliable source for the generation of biomarkers to diagnose and monitor ocular surface disease.
Rao P, Lertjirachai I, Yonekawa Y, Hasbrook M, Thomas BJ, Wood EH, Mehta N, Mane G, Drenser KA, Trese MT, Capone A. ETIOLOGY AND CLINICAL CHARACTERISTICS OF MACULAR EDEMA IN PATIENTS WITH FAMILIAL EXUDATIVE VITREORETINOPATHY. Retina 2020;40(7):1367-1373.Abstract
PURPOSE: To describe the etiology and clinical characteristics of macular edema (ME) in patients with familial exudative vitreoretinopathy. METHODS: Observational, retrospective case series of 30 patients (34 eyes) with ME and familial exudative vitreoretinopathy who underwent spectral-domain optical coherence tomography imaging between 2009 and 2016. Baseline and follow-up optical coherence tomographies were correlated with color fundus photography and fluorescein angiography. RESULTS: The average age was 20.6 years (6.6-68.7). Eighteen eyes exhibited cystoid ME (52.9%), 14 noncystoid ME (41.2%), and 2 eyes (5.9%) with both. Macular edema was foveal in 52.9% (n = 18). Eighteen of 24 eyes (64.3%) with an available fluorescein angiography showed leakage from ME. The most common structural feature was posterior hyaloidal organization/contraction (n = 15). Sixteen eyes were treated with topical or intravitreal steroids (n = 6), intravitreal anti-vascular endothelial growth factor (n = 3), or pars plana vitrectomy with membrane stripping (n = 7). There was no difference between mean preoperative and postoperative LogMAR visual acuity (0.63 [20/85] vs. 0.87 [20/148], P = 0.35) after vitrectomy despite a statistical improvement in the mean central foveal thickness (596 mm vs. 303 mm, P = 0.04). CONCLUSION: Macular edema in familial exudative vitreoretinopathy occurs most commonly because of traction. Vitrectomy is effective for relieving tractional forces with anatomical improvement.
Lally DR, Kasetty MA. CLOSURE OF SMALL MACULAR HOLES USING VITRECTOMY SURGERY WITH INTERNAL LIMITING MEMBRANE PEELING WITHOUT THE USE OF INTRAOCULAR GAS TAMPONADE: BROADENING THE UNDERSTANDING OF THE MACULAR HOLE PATHOPHYSIOLOGY. Retin Cases Brief Rep 2020;14(2):104-109.Abstract
PURPOSE: To determine whether small macular hole closure can be achieved with 25-G vitrectomy surgery with internal limiting membrane peeling without the use of intraocular gas tamponade or facedown positioning. METHODS: 25-G vitrectomy surgery with internal limiting membrane peeling without the use of intraocular gas tamponade or positioning was performed on 20 eyes with a small (<400-µm diameter), full-thickness macular hole. RESULTS: In 17 of 20 eyes (85%), the hole had closed. Three holes had closed by Postoperative Day 1, 13 holes by Postoperative Week 1, 16 holes by Postoperative Week 2, and 17 holes by Postoperative Week 6. At Postoperative Month 1, vision improved in 16 of 17 eyes in which the macular hole had closed. One hole that had not closed at the first postoperative week and two holes that had not closed at the third postoperative week required follow-up surgery with intraocular gas tamponade and facedown positioning, after which the hole closed. The mean preoperative visual acuity was 0.626 logMAR (20/85), and the mean postoperative visual acuity after 1 month was 0.392 logMAR (20/50) (P < 0.001). CONCLUSION: Vitrectomy surgery with internal limiting membrane peeling without the use of gas tamponade or positioning can achieve closure of small macular holes.
Thomas MG, Maconachie GDE, Constantinescu CS, Chan W-M, Barry B, Hisaund M, Sheth V, Kuht HJ, Dineen RA, Harieaswar S, Engle EC, Gottlob I. Congenital monocular elevation deficiency associated with a novel gene variant. Br J Ophthalmol 2020;104(4):547-550.Abstract
BACKGROUND: The genetic basis of monocular elevation deficiency (MED) is unclear. It has previously been considered to arise due to a supranuclear abnormality. METHODS: Two brothers with MED were referred to Leicester Royal Infirmary, UK from the local opticians. Their father had bilateral ptosis and was unable to elevate both eyes, consistent with the diagnosis of congenital fibrosis of extraocular muscles (CFEOM). Candidate sequencing was performed in all family members. RESULTS: Both affected siblings (aged 7 and 12 years) were unable to elevate the right eye. Their father had bilateral ptosis, left esotropia and bilateral limitation of elevation. Chin up head posture was present in the older sibling and the father. Bell's phenomenon and vertical rotational vestibulo-ocular reflex were absent in the right eye for both children. Mild bilateral facial nerve palsy was present in the older sibling and the father. Both siblings had slight difficulty with tandem gait. MRI revealed hypoplastic oculomotor nerve. Left anterior insular focal cortical dysplasia was seen in the older sibling. Sequencing of revealed a novel heterozygous variant (c.1263G>C, p.E421D) segregating with the phenotype. This residue is in the C-terminal H12 α-helix of β-tubulin and is one of three putative kinesin binding sites. CONCLUSION: We show that familial MED can arise from a variant and could be considered a limited form of CFEOM. Neurological features such as mild facial palsy and cortical malformations can be present in patients with MED. Thus, in individuals with congenital MED, consideration may be made for mutation screening.
Douglas VP, Douglas KA, Rizzo JF, Chwalisz BK. Case report: Orbital myositis triggering oxygen-responsive cluster headache. Cephalalgia 2020;40(3):313-316.Abstract
BACKGROUND: Orbital myositis is an idiopathic, non-infectious condition, typically seen in young females and usually affecting one extraocular muscle. Orbital myositis mimicking cluster headache is a rare clinical entity, and this is the first description of a case of a secondary trigeminal autonomic cephalalgia from orbital myositis responsive to high-flow oxygen. CASE: A young woman presented with new-onset, oxygen-responsive headache, periorbital pain and autonomic features. She had associated vertical diplopia on downgaze and subtle ocular misalignment. An initial diagnosis of cluster headache was made. Initial brain MRI was unrevealing, but dedicated MRI of the orbits showed enhancement of orbital muscles. The diplopia and the imaging findings were consistent with orbital myositis. CONCLUSION: Orbital myositis mimicking cluster headache is rare, and not previously reported as an oxygen-responsive headache.
Banks C, Scangas GA, Husain Q, Hatton MP, Fullerton Z, Metson R. The role of routine nasolacrimal sac biopsy during endoscopic dacryocystorhinostomy. Laryngoscope 2020;130(3):584-589.Abstract
OBJECTIVES/HYPOTHESIS: Most patients who undergo endoscopic dacryocystorhinostomy (DCR) have a diagnosis of idiopathic nasolacrimal duct obstruction. The purpose of this study was to examine the impact of routine biopsy of the lacrimal sac performed at time of DCR on subsequent patient diagnosis and treatment. STUDY DESIGN: Retrospective review. METHODS: The histopathology of nasolacrimal specimens (n = 769), obtained from 654 consecutive patients undergoing endoscopic DCR by a single surgeon over a 30-year period, were reviewed. Specific focus included the identification of unanticipated pathologic findings as they related to pertinent patient demographics, clinical presentation, radiologic findings, and intraoperative observations. RESULTS: The study population was 69.6% female, with an average age of 56.1 ± 18.2 years. Pathological findings of tissue from the nasolacrimal sac, which was routinely sampled in all cases, showed inflammation (n = 566 [73.6%]), normal histology (n = 147 [19.1%]), granulomas (n = 8 [1.0%]), and neoplastic process (n = 7 [0.9%]). Patient history, preoperative CT scan, and/or intraoperative findings alerted the surgeon to the possibility of an unusual diagnosis in 12 of the 15 patients. An unsuspected neoplastic or granulomatous cause of lacrimal obstruction was identified on intraoperative biopsy in three patients (0.46%). CONCLUSIONS: Although neoplastic and granulomatous diseases are relatively rare causes of lacrimal obstruction necessitating DCR surgery, they may be identified by through patient evaluation in most cases and by routine intraoperative biopsy of the lacrimal sac in all cases. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:584-589, 2020.
Zieske JD, Hutcheon AEK, Guo X. Extracellular Vesicles and Cell-Cell Communication in the Cornea. Anat Rec (Hoboken) 2020;303(6):1727-1734.Abstract
One question that has intrigued cell biologists for many years is, "How do cells interact to influence one another's activity?" The discovery of extracellular vesicles (EVs) and the fact that they carry cargo, which directs cells to undergo changes in morphology and gene expression, has revolutionized this field of research. Little is known regarding the role of EVs in the cornea; however, we have demonstrated that EVs isolated from corneal epithelial cells direct corneal keratocytes to initiate fibrosis. Intriguingly, our data suggest that EVs do not penetrate epithelial basement membrane (BM), perhaps providing a mechanism explaining the importance of BM in the lack of scarring in scrape wounds. Since over 100-million people worldwide suffer from visual impairment as a result of corneal scarring, the role of EVs may be vital to understanding the mechanisms of wound repair. Therefore, we investigated EVs in ex vivo and in vivo-like three-dimensional cultures of human corneal cells using transmission electron microscopy. Some of the major findings were all three major cell types (epithelial, fibroblast, and endothelial cells) appear to release EVs, EVs can be identified using TEM, and EVs appeared to be involved in cell-cell communication. Interestingly, while our previous publication suggests that EVs do not penetrate the epithelial BM, it appears that EVs penetrate the much thicker endothelial BM (Descemet's membrane). These findings indicate the huge potential of EV research in the cornea and wound healing, and suggest that during homeostasis the endothelium and stromal cells are in communication. Anat Rec, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
Lizano P, Bannai D, Lutz O, Kim LA, Miller J, Keshavan M. A Meta-analysis of Retinal Cytoarchitectural Abnormalities in Schizophrenia and Bipolar Disorder. Schizophr Bull 2020;46(1):43-53.Abstract
BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are characterized by reductions in gray matter and white matter. Limitations in brain imaging have led researchers to use optical coherence tomography (OCT) to explore retinal imaging biomarkers of brain pathology. We examine the retinal layers that may be associated with SZ or BD. METHODS: Articles identified using PubMed, Web of Science, Cochrane Database. Twelve studies met inclusion for acutely/chronically ill patients. We used fixed or random effects meta-analysis for probands (SZ and BD), SZ or BD eyes vs healthy control (HC) eyes. We adjusted for sources of bias, cross-validated results, and report standardized mean differences (SMD). Statistical analysis performed using meta package in R. RESULTS: Data from 820 proband eyes (SZ = 541, BD = 279) and 904 HC eyes were suitable for meta-analysis. The peripapillary retinal nerve fiber layer (RNFL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 12, SMD = -0.74, -0.51, -1.06, respectively). RNFL thinning was greatest in the nasal, temporal, and superior regions. The combined peripapillary ganglion cell layer and inner plexiform layer (GCL-IPL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 4, SMD = -0.39, -0.44, -0.28, respectively). No statistically significant differences were identified in other retinal or choroidal regions. Clinical variables were unrelated to the RNFL or GCL-IPL thickness by meta-regression. CONCLUSION: The observed retinal layer thinning is consistent with the classic gray- and white-matter atrophy observed on neuroimaging in SZ and BD patients. OCT may be a useful biomarker tool in studying the neurobiology of psychosis.
Wiegand I, Wolfe JM. Age doesn't matter much: hybrid visual and memory search is preserved in older adults. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2020;27(2):220-253.Abstract
We tested younger and older observers' attention and long-term memory functions in a "hybrid search" task, in which observers look through visual displays for instances of any of several types of targets held in memory. Apart from a general slowing, search efficiency did not change with age. In both age groups, reaction times increased linearly with the visual set size and logarithmically with the memory set size, with similar relative costs of increasing load (Experiment 1). We replicated the finding and further showed that performance remained comparable between age groups when familiarity cues were made irrelevant (Experiment 2) and target-context associations were to be retrieved (Experiment 3). Our findings are at variance with theories of cognitive aging that propose age-specific deficits in attention and memory. As hybrid search resembles many real-world searches, our results might be relevant to improve the ecological validity of assessing age-related cognitive decline.

Pages