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Kühn T, Rohrmann S, Karavasiloglou N, Friedman DS, Cassidy A, Bärnighausen T, Schuster AK, Nickels S. Glaucoma and mortality risk: findings from a prospective population-based study. Sci Rep 2021;11(1):11771.Abstract
Glaucoma is a neurodegenerative disease with a structural change of the optic nerve head, leading to visual field defects and ultimately blindness. It has been proposed that glaucoma is associated with increased mortality, but previous studies had methodological limitations (selective study samples, lack of data on potential confounders, self-reported or secondary data on glaucoma diagnoses). We evaluated the association between diagnosed glaucoma and mortality in the population-based National Health and Nutrition Examination Survey (NHANES), a representative health survey in the United States. The survey cycles 2005-2006 and 2007-2008 included an extensive ophthalmic examination with fundus photography, which were used to derive standardized glaucoma diagnoses. Risk of all-cause mortality was assessed with multivariable Cox proportional hazards regression models accounting for the complex survey design of NHANES. Time to death was calculated from the examination date to date of death or December 31, 2015 whichever came first. 5385 participants (52.5% women) were eligible, of which 138 had glaucoma at baseline, and 833 died during follow-up. Participants with glaucoma were more likely to be older than those without glaucoma (mean age 69.9 vs. 56.0 years). Mean follow-up time was 8.4 years for participants with glaucoma, and 8.6 years for participants without glaucoma. Glaucoma was associated with increased mortality in an unadjusted Cox regression model (hazard ratio 2.06, 95% confidence interval 1.16 to 3.66), but the association was no longer statistically significant after adjusting for age and sex (hazard ratio 0.74, 95% confidence interval 0.46 to 1.17). Additional adjustment for a range of potential confounders did not significantly change the results. In this representative population-based study, we found no evidence of increased mortality risk in glaucoma patients.
Makuloluwa AK, Hamill KJ, Rauz S, Bosworth L, Haneef A, Romano V, Williams RL, Dartt DA, Kaye SB. The conjunctival extracellular matrix, related disorders and development of substrates for conjunctival restoration. Ocul Surf 2021;Abstract
The conjunctiva can be damaged by numerous diseases with scarring, loss of tissue and dysfunction. Depending on extent of damage, restoration of function may require a conjunctival graft. A wide variety of biological and synthetic substrates have been tested in the search for optimal conditions for ex vivo culture of conjunctival epithelial cells as a route toward tissue grafts. Each substrate has specific advantages but also disadvantages related to their unique physical and biological characteristics, and identification and development of an improved substrate remains a priority. To achieve the goal of mimicking and restoring a biological material, requires information from the material. Specifically, extracellular matrix (ECM) derived from conjunctival tissue. Knowledge of the composition and structure of native ECM and identifying contributions of individual components to its function would enable using or mimicking those components to develop improved biological substrates. ECM is comprised of two components: basement membrane secreted predominantly by epithelial cells containing laminins and type IV collagens, which directly support epithelial and goblet cell adhesion differentiation and growth and, interstitial matrix secreted by fibroblasts in lamina propria, which provides mechanical and structural support. This review presents current knowledge on anatomy, composition of conjunctival ECM and related conjunctival disorders. Requirements of potential substrates for conjunctival tissue engineering and transplantation are discussed. Biological and synthetic substrates and their components are described in an accompanying review.
Boal NS, Cretara EAZ, Bleier BS, Lam AC, Lefebvre DR. In vivo analysis of endocanalicular light pipe transillumination in endoscopic dacryocystorhinostomy: Anatomic considerations and cautions for the transitioning. Orbit 2021;:1-5.Abstract
Purpose: Localization of the lacrimal sac is a critical step during endoscopic dacryocystorhinostomy (endo-DCR). A "light pipe" can be used to transilluminate the lacrimal sac endonasally. We hypothesized that this may misguide the surgeon learning endo-DCR to create an osteotomy mostly posterior to the maxillary line if only the bone overlying the transillumination was to be removed, as the thinner lacrimal bone will transmit light more readily than the thicker maxillary bone of the frontal process of the maxilla that forms the anterior lacrimal sac fossa.Methods: The charts of 32 patients with primary acquired nasolacrimal duct obstruction in whom a lighted system was used during endo-DCR at Massachusetts Eye and Ear from April 2015 through October 2016 were reviewed. Patients with prior history of lacrimal surgery or trauma directly to the lacrimal sac fossa were excluded. Location of the maximal point of transillumination in relation to the maxillary line was observed and noted intraoperatively.Results: Of a total of 39 endo-DCR surgeries performed, the intraoperative transillumination point was entirely posterior to the maxillary line in 32 instances (82%).Conclusions: Use of an endocanalicular light pipe preferentially illuminates posterior to the maxillary line endonasally. The anterior lacrimal sac fossa (maxillary line and anterior as visualized endonasally) is rarely transilluminated, likely due to thicker bone in that region. Surgeons learning how to perform endo-DCR using a light pipe should be aware of this phenomenon.
Diel RJ, Mehra D, Kardon R, Buse DC, Moulton E, Galor A. Photophobia: shared pathophysiology underlying dry eye disease, migraine and traumatic brain injury leading to central neuroplasticity of the trigeminothalamic pathway. Br J Ophthalmol 2021;105(6):751-760.Abstract
BACKGROUND: Photophobia is a potentially debilitating symptom often found in dry eye disease (DE), migraine and traumatic brain injury (TBI). METHODS: We conducted a review of the literature via a PubMed search of English language articles with a focus on how photophobia may relate to a shared pathophysiology across DE, migraine and TBI. RESULTS: DE, migraine and TBI are common conditions in the general population, are often comorbid, and share photophobia as a symptom. Across the three conditions, neural dysregulation of peripheral and central nervous system components is implicated in photophobia in various animal models and in humans. Enhanced activity of the neuropeptide calcitonin gene-related peptide (CGRP) is closely linked to photophobia. Current therapies for photophobia include glasses which shield the eyes from specific wavelengths, botulinum toxin, and inhibition of CGRP and its receptor. Many individuals have persistent photophobia despite the use of these therapies, and thus, development of new therapies is needed. CONCLUSIONS: The presence of photophobia in DE, migraine and TBI suggests shared trigeminothalamic pathophysiologic mechanisms, as explained by central neuroplasticity and hypersensitivity mediated by neuropeptide CGRP. Treatment strategies which target neural pathways (ie, oral neuromodulators, transcutaneous nerve stimulation) should be considered in patients with persistent photophobia, specifically in individuals with DE whose symptoms are not controlled with traditional therapies.
Yuan A, Ma K, Sharifi S, Pineda R. Biomechanical testing of flanged polypropylene sutures in scleral fixation. Am J Ophthalmol 2021;Abstract
OBJECTIVE: To optimize the flanged belt-loop technique of scleral fixation through biomechanical testing and report clinical outcomes of resultant modifications. DESIGN: Experimental study. METHODS: The force to disinsert flanged polypropylene suture from human cadaveric sclera was assessed using a tensile testing machine and compared to the breaking strengths of 9-0 and 10-0 polypropylene. The effects of modifying suture gauge (5-0, 6-0, 7-0 or 8-0), amount of suture cauterized (0.5 or 1.0mm), and sclerotomy size (27-, 30-, 32-, 33-gauge) were investigated. Belt-loop intrascleral fixation using 6-0 and 7-0 polypropylene with 30- and 32-gauge needles respectively was performed in 5 patients. MAIN OUTCOME MEASURES: Flanged suture disinsertion force in cadaveric sclera. RESULTS: The average force to disinsert a flange created by melting 1.0mm of 5-0, 6-0, 7-0 and 8-0 polypropylene suture from human cadaveric sclera via 27-, 30-, 32- and 33-gauge needle sclerotomies was 3.0 ± 0.5N, 2.1 ± 0.3N, 0.9 ± 0.2N and 0.4 ± 0.1N respectively. The disinsertion forces for flanges formed by melting 0.5mm of the same gauges were 72-79% lower (p < 0.001). In comparison, the breaking strengths of 9-0 and 10-0 polypropylene were 1.0 ± 0.2N and 0.5 ± 0.0N. Belt-loop fixation using 6-0 and 7-0 polypropylene with 30- and 32-gauge sclerotomies demonstrated good outcomes at 6 months. CONCLUSIONS: The flanged belt-loop technique is a biomechanically sound method of scleral fixation using 1.0mm flanges of 5-0 to 7-0 polypropylene paired with 27-, 30- and 32- gauge sclerotomies. In contrast, 8-0 polypropylene and 0.5 mm flanges of any suture gauge will likely be unstable with this technique.
Singh RB, Liu L, Anchouche S, Yung A, Mittal SK, Blanco T, Dohlman TH, Yin J, Dana R. Ocular redness - I: Etiology, pathogenesis, and assessment of conjunctival hyperemia. Ocul Surf 2021;21:134-144.Abstract
The translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation of the conjunctival microvasculature consisting of extensive branching of superficial and deep arterial systems and corresponding drainage pathways, and the translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation. Conjunctival hyperemia is caused by a pathological vasodilatory response of the microvasculature in response to inflammation due to a myriad of infectious and non-infectious etiologies. It is one of the most common contributors of ocular complaints that prompts visits to medical centers. Our understanding of these neurogenic and immune-mediated pathways has progressed over time and has played a critical role in developing targeted novel therapies. Due to a multitude of underlying etiologies, patients must be accurately diagnosed for efficacious management of conjunctival hyperemia. The diagnostic techniques used for the grading of conjunctival hyperemia have also evolved from descriptive and subjective grading scales to more reliable computer-based objective grading scales.
Lonial S, Nooka AK, Thulasi P, Badros AZ, Jeng BH, Callander NS, Potter HA, Sborov D, Zaugg BE, Popat R, Esposti SD, Byrne J, Opalinska J, Baron J, Piontek T, Gupta I, Dana R, Farooq AV, Colby K, Jakubowiak A. Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM). Blood Cancer J 2021;11(5):103.Abstract
Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit-risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.
Godfrey D, Torres A, Heidary G, Zahoor H, Lee A, Berry G, Engle E. A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome. Ophthalmic Genet 2021;42(5):612-614.Abstract
Background: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome.Patient and methods: We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking.Results: Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures.Conclusion: This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.
Olson HE, Costantini JG, Swanson LC, Kaufmann WE, Benke TA, Fulton AB, Hansen R, Poduri A, Heidary G. Cerebral visual impairment in CDKL5 deficiency disorder: vision as an outcome measure. Dev Med Child Neurol 2021;63(11):1308-1315.Abstract
AIM: To characterize the neuro-ophthalmological phenotype of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) and assess visual acuity as a reproducible, quantitative outcome measure. METHOD: We retrospectively analyzed clinical data from patients with CDD. Complete neuro-ophthalmological assessments, including visual acuity, were evaluated. RESULTS: Of 26 patients (22 females, four males; median age 4y, interquartile range 2y 1mo-7y 10mo), cerebral visual impairment (CVI), defined as visual dysfunction in the absence of ocular or anterior visual pathway abnormalities, was diagnosed in all those over 2 years of age. Ophthalmological examinations revealed nystagmus in 10 patients and strabismus in 24 patients. Visual acuity was measured in 24 patients, by preferential looking in all and by sweep visual evoked potential in 13. Visual acuities were lower than age expectations and demonstrated improvement in the first 3 years. Adjusting for age and sex, average preferential looking visual acuity after 2 years of age was higher in patients with intact mobility than in those who were non-mobile. INTERPRETATION: CVI was observed in patients with CDD. Visual acuity improved over time and correlated with mobility. Visual acuity, as a quantifiable measure of visual function, should be considered as an outcome measure in pre-clinical and clinical studies for CDD. What this paper adds Cerebral visual impairment is highly prevalent in cyclin-dependent kinase-like 5 deficiency disorder (CDD). Visual acuity is a measurable quantitative outcome measure in CDD. Visual acuity in CDD correlates with gross motor ability.
E J-Y, Mihailovic A, Garzon C, Schrack JA, Li T, West SK, Friedman DS, Gitlin LN, Ramulu PY. Importance and severity dependence of physical activity by GPS-tracked location in glaucoma patients: GPS-tracked physical activity in glaucoma. Am J Ophthalmol 2021;Abstract
PURPOSE: To quantify the association of visual field (VF) damage on physical activity away-from-home, per away-from-home excursion, and at home. DESIGN: Prospective cohort study. METHODS: Among 229 participants with glaucoma or suspected glaucoma, severity of VF damage was defined as average sensitivity within the integrated VF (IVF). Participants wore accelerometers and GPS trackers for seven days to measure physical activity and characterize activity location. Multivariable negative binomial regressions were used to test whether away-from-home activity per day, physical activity per away-from-home excursion, and at home activity per day varied by severity of VF damage. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with a lower amount of away-from-home activities per day [18% less Moderate & Vigorous Physical Activity (MVPA) minutes/day, 95% CI, 0.69 to 0.97], and physical activities per away-from-home excursion (20% less MVPA minutes/excursion, 95% CI, 0.65, 0.98). Similar findings were noted for other away-from-home activity measures (including active minutes/steps per day, or active minutes/steps per excursion). However, worse IVF sensitivity was not associated with measures of at home activities (MVPA minutes/day, active minutes/day, and steps/day), time spent at or away from home, or excursions/week (p>0.1 for all). CONCLUSIONS: Restriction of physical activity in more severe glaucoma patients results mostly from activity restriction outside home environment. These findings highlight the importance of maintaining a safe home environment (where activity is less restricted) and increasing confidence to perform activity, particular high intensity activity, when leaving the home amongst patients with glaucoma.
Ciociola EC, Kavitha S, Sengupta S, Wiggs JL, Kader MA, Raman GV, Rajendrababu S, Ramulu PY, Venkatesh R, Zebardast N. The Heritability of Primary Angle Closure Anatomic Traits and Predictors of Angle Closure in South Indian Siblings. Am J Ophthalmol 2021;Abstract
PURPOSE: To estimate the heritability of ocular biometric and anterior chamber morphologic parameters and to determine predictors of angle closure concordance in South Indian probands with angle closure and their siblings. DESIGN: Prospective observational cohort study. METHODS: Subjects received a standardized ophthalmic examination, A-scan ultrasonography, pachymetry, and anterior segment optical coherence tomography (ASOCT) imaging. Heritability was calculated using residual correlation coefficients adjusted for age, sex, and home setting. Concordant siblings pairs were defined as both proband and sibling with angle closure. Predictors of angle closure concordance among siblings were calculated using multivariable logistic regression models. RESULTS: 345 sibling pairs participated. All anterior chamber parameters were highly heritable (p<0.001 for all). Similarly, all iris parameters, axial length, lens thickness (LT), central corneal thickness, anterior lens curvature, lens vault (LV), spherical equivalent, and intraocular pressure were moderately to highly heritable (p<0.004 for all). LV and LT were more heritable among concordant siblings (p<0.05 for both). In contrast, ASOCT angle parameters had statistically insignificant heritability estimates. In multivariable analyses, siblings older than their probands were more likely to be concordant for angle closure (OR=1.05 (95% CI 1.01, 1.09), p=0.02) and siblings with deeper anterior chamber depths (ACD) compared to their proband were less likely to be concordant for angle closure (OR=0.74 (95% CI 0.64, 0.86), p<0.001). CONCLUSIONS: Iris, anterior chamber, and lens parameters may be heritable while angle parameters were not. LT and LV may play important roles in the pathogenesis of angle closure. Siblings who are older or have a shallower ACD may need more careful disease monitoring.
Chen ZJ, Lu SY, Rong SS, Ho M, Ng DS-C, Chen H, Gong B, Yam JC, Young AL, Brelen M, Tham CC, Pang CP, Chen LJ. Genetic associations of central serous chorioretinopathy: a systematic review and meta-analysis. Br J Ophthalmol 2021;Abstract
AIMS: To identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: We searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias. RESULTS: Totally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80×10-5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44×10-15). Among them, only TNFRSF10A rs13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2 and CFH showed opposite trends in the SNP associations. CONCLUSIONS: This study confirmed the associations of ARMS2, CFH and TNFRSF10A with CSCR, and revealed that ARMS2, CFH and TNFRSF10A may affect different phenotypic expressions of CSCR, nAMD and PCV.
Li Y, Hall NE, Pershing S, Hyman L, Haller JA, Lee AY, Lee CS, Chiang M, Lum F, Miller JW, Lorch A, Elze T. Age, Gender, and Laterality of Retinal Vascular Occlusion: A Retrospective Study from the IRIS® Registry. Ophthalmol Retina 2021;Abstract
PURPOSE: Retinal vascular occlusion is a leading cause of profound irreversible visual loss, but the understanding of the disease is insufficient. We systematically investigated the age, gender, and laterality at the onset of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) in the IRIS® Registry (Intelligent Research in Sight). DESIGN: A retrospective registry cohort. PARTICIPANTS: Retinal vascular occlusion cases participating in the IRIS Registry. METHODS: All cases diagnosed as retinal vascular occlusion in the IRIS Registry between 2013 and 2017 were included. Cases with unspecified gender or laterality were excluded when conducting the relevant analyses. Cases were categorized based on diagnosis codes into RAO, with subtypes transient retinal artery occlusion (TRAO), partial retinal artery occlusion (PRAO), branch retinal artery occlusion (BRAO), and central retinal artery occlusion (CRAO), and into RVO, with subtypes venous engorgement (VE), branch retinal vein occlusion (BRVO), and central retinal vein occlusion (CRVO). Age was evaluated as a categorical variable (5-year increments). We investigated the association of age, gender, and laterality with the onset frequency of retinal vascular occlusion subtypes. MAIN OUTCOME MEASURES: The frequency of onset of RAO and RVO subtypes by age, gender and laterality. RESULTS: A total of 1,251,476 retinal vascular occlusion cases were included, 23.8% of which were RAO, while 76.2% were RVO. 1,248,656 and 798,089 cases were selected for analysis relevant to gender and laterality, respectively. The onset frequency of all subtypes increased with age. PRAO, BRAO, CRAO, and CRVO presented more frequently in men (53.5%, 51.3%, 52.6%, 50.4%), while TRAO, VE, and BRVO presented more frequently in women (54.9%, 56.0%, 54.5%). BRVO and all RAO subtypes showed a right-eye onset preference (BRVO 51.0%, TRAO 51.7%, PRAO 54.4%, BRAO 53.5%, CRAO 53.4%), while VE and CRVO exhibited a left-eye onset preference (VE 53.3%, CRVO 50.9%). CONCLUSIONS: While retinal vascular occlusion incidence increases with age regardless of subtypes, we found various subtype-specific disease onset differences related to gender and, in particular, ocular laterality. These findings may improve understanding of the specific etiology of retinal vascular occlusions of different subtypes and their relationship with structural and anatomic asymmetries of the vascular system.

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