April 2022

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Bispo PJM, Sahm DF, Asbell PA. A Systematic Review of Multi-decade Antibiotic Resistance Data for Ocular Bacterial Pathogens in the United States. Ophthalmol Ther 2022;11(2):503-520.Abstract
INTRODUCTION: Since 2009, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study has been assessing in vitro antibiotic resistance for bacterial isolates sourced from ocular infections in the US. The main goal of this systematic review was to compare in vitro resistance data for ocular pathogens from published US studies with the most recently published data from the ARMOR study (2009-2018) and, where possible, to evaluate trends in bacterial resistance over time over all studies. METHODS: A literature search was conducted using MEDLINE®, BIOSIS Previews®, and EMBASE® databases (1/1/1995-6/30/2021). Data were extracted from relevant studies and antibiotic susceptibility rates for common ocular pathogens (Staphylococcus aureus, coagulase-negative staphylococci [CoNS], Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae), longitudinal changes in susceptibility, and multidrug resistance (MDR) were compared descriptively. RESULTS: Thirty-two relevant studies were identified. High in vitro resistance was found among S. aureus and CoNS to fluoroquinolones, macrolides, and methicillin/oxacillin across studies, with high rates of MDR noted, specifically among methicillin-resistant staphylococci. Data from studies pre-dating or overlapping the early years of ARMOR reflected increasing rates of S. aureus resistance to fluoroquinolones, macrolides, methicillin/oxacillin, and aminoglycosides, while the ARMOR data suggested slight decreases in resistance to these classes between 2009 and 2018. Overall, methicillin-resistant S. aureus (MRSA) prevalence peaked from 2005 to 2015 with a possible decreasing trend in more recent years. DISCUSSION AND CONCLUSIONS: Data from local and regional US datasets were generally consistent with data from the national ARMOR surveillance study. Continued surveillance of ocular bacterial pathogens is needed to track trends such as methicillin resistance and MDR prevalence and any new emerging antibiotic resistance phenotypes. Susceptibility data from ARMOR can inform initial choice of therapy, especially in practice areas where local antibiograms are unavailable.
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Chinn RN, Raghuram A, Curtiss MK, Gehring AM, De Paula AJ, Roberts TL. Repeatability of the Accommodative Response Measured by the Grand Seiko Autorefractor in Children With and Without Amblyopia and Adults. Am J Ophthalmol 2022;236:221-231.Abstract
PURPOSE: To assess test-retest repeatability of the accommodative response (AR) in children with and without amblyopia and adults using the Grand Seiko autorefractor. DESIGN: Prospective reliability assessment. METHODS: Test-retest of accommodation was obtained while participants viewed 20/150 sized letters at 33 cm using the Grand Seiko autorefractor in children 5 to <11 years with amblyopia (n=24) and without amblyopia (n=36), and adults 18 to <35 years (n=34). Bland-Altman 95% limits of agreement (LOA) and intraclass correlation coefficients (ICCs) were used to assess repeatability and reliability. The AR between the fellow and amblyopic eyes of children with amblyopia and eye 1 and eye 2 of the visually normal participants was assessed using group comparisons. RESULTS: The 95% LOA of the AR was greatest in the amblyopic eyes (-1.25 diopters [D], 1.62 D) of children with amblyopia. The 95% LOA were similar between the fellow eyes (-0.88 D, 0.74 D) of children with amblyopia and both eyes of the children without amblyopia (eye 1: -0.68 D, 0.71 D; eye 2: -0.59 D, 0.70 D) and the adults (eye 1: 95% LOA = -0.49 D, 0.45 D; eye 2: LOA = -0.66 D, 0.67 D). ICCs revealed the Grand Seiko autorefractor as a reliable instrument for measuring AR. CONCLUSIONS: The Grand Seiko autorefractor was more repeatable and reliable when measuring the AR in children and adults without amblyopia than in the amblyopic eye in children with amblyopia. It is recommended that multiple measures of the AR be obtained in amblyopic eyes to improve the precision of measures.
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Doshi H, Solli E, Elze T, Pasquale LR, Wall M, Kupersmith MJ. Unsupervised Machine Learning Shows Change in Visual Field Loss in the Idiopathic Intracranial Hypertension Treatment Trial. Ophthalmology 2022;Abstract
PURPOSE: We previously reported that archetypal analysis (AA), a type of unsupervised machine learning, identified and quantified patterns of visual field (VF) loss in idiopathic intracranial hypertension (IIH), referred to as archetypes (ATs). We assessed whether AT weight changes over time are consistent with changes in conventional global indices. We explored whether visual outcome or treatment effects are associated with select ATs and whether AA reveals residual VF defects in eyes deemed "normal" after treatment. DESIGN: Analysis of data collected from a randomized controlled trial. PARTICIPANTS: 2,862 VFs taken from 165 participants during the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: We applied a 14-AT model derived from IIHTT VFs. We examined changes in individual AT weights over time within all study eye VFs and evaluated differences between treatment groups. We created an AT Change score to assess overall VF change from baseline. We tested threshold baseline AT weights for association with VF outcome and treatment effect at six months. We determined the abnormal ATs with meaningful weight at outcome for VFs considered "normal" based on a mean deviation (MD) cutoff ≥-2.00 dB. MAIN OUTCOME MEASURES: Individual AT weighting coefficients, MD. RESULTS: AT1 (a normal VF pattern) showed the greatest weight change for all study eyes, increasing from 11.9% (interquartile range [IQR]: 0.44-24.1%) at baseline to 31.2% (IQR: 16.0-45.5%) at outcome (p<0.001). AT1 weight change (r=0.795, p<0.001) and a global score of AT change (r=0.988, p<0.001) correlated strongly with MD change. Study eyes with baseline AT2 (a mild diffuse VF loss pattern) weight ≥ 44% (≥1 standard deviation above the mean) showed higher AT2 weights at outcome than those with AT2 < 44% at baseline (p<0.001). Only the latter group showed a significant acetazolamide treatment effect. AA revealed residual VF loss patterns, most frequently representing mild diffuse loss and enlarged blind spot in 64 of 66 study eyes with MD ≥-2.00 dB at outcome. CONCLUSION: AA provides a quantitative approach to monitoring VF changes in IIH. Baseline AT features may be associated with treatment response and VF outcome. AA uncovers residual VF defects not otherwise revealed by MD.
Douglas VP, Douglas KA, Vavvas DG, Miller JW, Miller JB. Short- and Long-Term Visual Outcomes in Patients Receiving Intravitreal Injections: The Impact of the Coronavirus 2019 Disease (COVID-19)-Related Lockdown. J Clin Med 2022;11(8)Abstract
Purpose: To investigate the short- and long-term impact of COVID-19-related lockdown on the vision of patients requiring intravitreal injections (IVI) for neovascular Age-related Macular degeneration (nvAMD), diabetic retinopathy (DR), central retinal vein occlusion (CRVO), or branch retinal vein occlusion (BRVO). Methods: This is a retrospective study from the Retina department of three Mass Eye and Ear centers. Charts of patients age of ≥ 18 years with any of the abovementioned diagnoses who had a scheduled appointment anytime between 17 March 2020 until 18 May 2020 (lockdown period in Boston, Massachusetts) were reviewed at baseline (up to 12 weeks before the lockdown), at first available follow-up (=actual f/u) during or after the lockdown period, at 3 months, 6 months, and at last available completed appointment of 2020. Results: A total of 1001 patients met the inclusion criteria. Of those patients, 479 (47.9%) completed their intended f/u appointment, while 522 missed it (canceled and "no show"). The delay in care of those who missed it was 59.15 days [standard deviation (SD) ± 49.6]. In these patients, significant loss of vision was noted at actual f/u [Best corrected visual acuity (BCVA) in LogMAR (Logarithm of the Minimum Angle of Resolution)-mean (±SD)-completed: 0.45 (±0.46), missed: 0.53 (±0.55); p = 0.01], which was more prominent in the DR group [Visual acuity (VA) change in LogMAR-mean (±SD); completed: 0.04 (±0.28), missed: 0.18 (±0.44); p = 0.02] and CRVO [completed: -0.06 (±0.27), missed: 0.11 (±0.35); p = &lt;0.001] groups followed by nvAMD [completed: 0.006 (±0.16), missed: 0.06 (±0.27); p = 0.004] and BRVO [completed: -0.02 (±0.1), missed: 0.03 (±0.14); p = 0.02] ones. Overall, a higher percent of people who missed their intended f/u experienced vision loss of more than 15 letters at last f/u compared to those who completed it [missed vs. completed; 13.4% vs. 7.4% in nvAMD (p = 0.72), 7.8% vs. 6.3% in DR (0.84), 15.5% vs. 9.9% in CRVO (p &lt; 0.001) and 9.6% vs. 2% in BRVO (p = 0.48)]. Conclusions: Delay in care of about 8.45 weeks can lead to loss of vision in patients who receive IVI with DR and CRVO patients being more vulnerable in the short-term, whereas in the long-term, CRVO patients followed by the nvAMD patients demonstrating the least vision recovery. BRVO patients were less likely to be affected by the delay in care. Adherence to treatment is key for maintaining and improving visual outcomes in patients who require IVI.
Douglas VP, Owji S, Pakravan M, Charoenkijkajorn C, Lee AG. McArdle Disease Rhabdomyolysis Precipitated by Acetazolamide for Idiopathic Intracranial Hypertension. J Neuroophthalmol 2022;
Douglas VP, Garg I, Douglas KA, Miller JB. Subthreshold Exudative Choroidal Neovascularization (CNV): Presentation of This Uncommon Subtype and Other CNVs in Age-Related Macular Degeneration (AMD). J Clin Med 2022;11(8)Abstract
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in people over the age of 50 worldwide. Exudative or neovascular AMD is a more severe subset of AMD which is characterized by the presence of choroidal neovascularization (CNV). Recent advancements in multimodal ophthalmic imaging, including optical coherence tomography (OCT) and OCT-angiography (OCT-A), have facilitated the detection and characterization of previously undetectable neovascular lesions and have enabled a more refined classification of CNV in exudative as well as nonexudative AMD patients. Subthreshold exudative CNV is a novel subtype of exudative AMD that typically presents asymptomatically with good visual acuity and is characterized by stable persistent or intermittent subretinal fluid (SRF). This review aims to provide an overview of the clinical as well as multimodal imaging characteristics of CNV in AMD, including this new clinical phenotype, and propose effective approaches for management.
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Elhusseiny AM, Traish AS, Saeed HN, Mantagos IS. Topical cenegermin 0.002% for pediatric neurotrophic keratopathy. Eur J Ophthalmol 2022;:11206721221094783.Abstract
PURPOSE: To evaluate the efficacy and safety of cenegermin 0.002% ophthalmic drops in the management of pediatric neurotrophic keratopathy (NK). METHODS: Retrospective chart review of children under the age of 18 years diagnosed with NK at Boston Children's Hospital/Massachusetts Eye and Ear Infirmary and treated with topical cenegermin 0.002% ophthalmic solution between June 2018 and June 2021 was performed. Data collection included etiology of NK, age at time of initiation of topical cenegermin, laterality, ethnicity, gender, history of previous ocular therapy, pre- and post-therapy best corrected visual acuity, pre- and post-therapy cornea examination, any adverse events from topical cenegermin, associated ocular conditions, and history of ocular surgeries. RESULTS: The current study includes four eyes of four pediatric patients with a mean age of 4.5 ± 2.0 years at the time of initiation of topical cenegermin therapy. The mean time from NK diagnosis until start of topical cenegermin drops was 5.2 ± 4.3 months and mean follow-up time was 15 ± 9.6 months. In all four patients, marked improvement in epitheliopathy was demonstrated after completion of therapy. Best corrected visual acuity was measurable in 3 eyes of 3 patients, and it improved from a mean of 0.07 ± 0.01 to a mean of 0.29 ± 0.26 (P = 0.3). No adverse events related to cenegermin therapy were noted. CONCLUSION: Topical cenegermin was effective in improving corneal healing for pediatric NK.
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Fjaervoll K, Fjaervoll H, Magno M, Nøland ST, Dartt DA, Vehof J, Utheim TP. Review on the possible pathophysiological mechanisms underlying visual display terminal-associated dry eye disease. Acta Ophthalmol 2022;Abstract
BACKGROUND: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described. PURPOSE: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED. METHODS: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated. FINDINGS: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development. CONCLUSION: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED.
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Gotti G, Stevenson K, Kay-Green S, Blonquist TM, Mantagos JS, Silverman LB, Place AE. Ocular abnormalities at diagnosis and after the completion of treatment in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Pediatr Blood Cancer 2022;69(4):e29542.Abstract
BACKGROUND: Ocular abnormalities (OA) in pediatric patients with acute lymphoblastic leukemia (ALL) are common findings both at diagnosis and later in follow-up. The frequency, predictors, and prognostic impact of OA in the context of recent ALL protocols are not well characterized. PROCEDURE: Single-center retrospective analysis of the medical records of 224 patients with ALL enrolled on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05-001. RESULTS: Overall, 217 (98%) patients had at least one ophthalmic exam. Retinal hemorrhages were the most frequent abnormalities at diagnosis (11%) and cataracts at later time points (13%). OA at diagnosis were associated with age ≥10 years and with the severity of anemia and thrombocytopenia; they were also univariately associated with lower 5-year event-free survival (EFS) (high risk [HR] = 3.09 [95% CI: 1.38-6.94]; p = .006), but not in a disease-free survival (DFS) model adjusted for end-induction minimal residual disease (p = .82). The cumulative incidence of cataract was 13.1% ± 2.8% at 43 months from diagnosis; its development was associated with high presenting white blood cell count (≥50,000/μl) (p = .010), male sex (p = .036), higher risk group (p = .025), and cranial radiation (p = .004). Cataract was associated with decreased visual acuity. CONCLUSIONS: OA at diagnosis, present in 12% of patients, were associated with older age, anemia, and thrombocytopenia and did not carry a significant prognostic impact. Cataracts were detected in over 10% of patients and were associated with decreased visual acuity, thus supporting routine screening after completion of therapy, especially for those treated with high-risk protocols.
Grotz S, Schäfer J, Wunderlich KA, Ellederova Z, Auch H, Bähr A, Runa-Vochozkova P, Fadl J, Arnold V, Ardan T, Veith M, Santamaria G, Dhom G, Hitzl W, Kessler B, Eckardt C, Klein J, Brymova A, Linnert J, Kurome M, Zakharchenko V, Fischer A, Blutke A, Döring A, Suchankova S, Popelar J, Rodríguez-Bocanegra E, Dlugaiczyk J, Straka H, May-Simera H, Wang W, Laugwitz K-L, Vandenberghe LH, Wolf E, Nagel-Wolfrum K, Peters T, Motlik J, Fischer DM, Wolfrum U, Klymiuk N. Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes. EMBO Mol Med 2022;14(4):e14817.Abstract
Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo.
for the Group WCPEDI, Hartnett EM, Wallace DK, Dean TW, Li Z, Boente CS, Dosunmu EO, Freedman SF, Golden RP, Kong L, Prakalapakorn GS, Repka MX, Smith LE, Wang H, Kraker RT, Cotter SA, Holmes JM. Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants. JAMA Ophthalmol 2022;140(4):337-344.Abstract
Importance: Intravitreal bevacizumab effectively treats severe retinopathy of prematurity (ROP), but it enters the bloodstream and may reduce serum vascular endothelial growth factor (VEGF), potentially causing detrimental effects on developing organs in the premature infant. Objective: To evaluate the association of intravitreal bevacizumab with plasma bevacizumab and VEGF concentrations at 2 and 4 weeks after predefined, de-escalating doses of intravitreal bevacizumab were administered to infants with severe ROP. Design, Setting, and Participants: This phase 1 dose de-escalation case series study was conducted at 10 US hospitals of ophthalmology institutions from May 21, 2015, to May 7, 2019. Blood samples were collected 2 and 4 weeks after intravitreal bevacizumab injection. Participants included 83 premature infants with type 1 ROP in 1 or both eyes and no previous ROP treatment. Data were analyzed from April 2017 to August 2021. Interventions: Study eyes received a single bevacizumab injection of 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. When the fellow eye required treatment, one dose higher was administered. Total dose administered at baseline was defined as the sum of doses given to each eye within 3 days of initial study-eye injection. Main Outcomes and Measures: Plasma bevacizumab concentration at 2 and 4 weeks after injection and the percentage change in plasma VEGF concentrations from pretreatment levels. Results: A total of 83 infants (mean [SD] age, 25 [2] weeks; 48 boys [58%]) were included in this study. Higher doses of bevacizumab administered at baseline were associated with higher plasma bevacizumab concentrations at 2 weeks (ρ, 0.53; 95% CI, 0.31-0.70) and 4 weeks (ρ, 0.44; 95% CI, 0.18-0.64). Plasma VEGF concentrations decreased by 50% or more from pretreatment levels in 40 of 66 infants (61%) at 2 weeks and 31 of 61 infants (51%) at 4 weeks, but no association was observed between the total dose of bevacizumab administered at baseline and percentage change in plasma VEGF concentrations 2 weeks (ρ, -0.04; 95% CI, -0.28 to 0.20) or 4 weeks (ρ, -0.17; 95% CI, -0.41 to 0.08) after injection. Conclusions and Relevance: Results of this phase 1 dose de-escalation case series study revealed that bevacizumab doses as low as 0.002 mg were associated with reduced plasma VEGF levels for most infants at 2 and 4 weeks after intravitreal administration; however, no association was observed between total bevacizumab dose administered and reductions in plasma VEGF levels from preinjection to 2 weeks or 4 weeks. Additional studies are needed to evaluate the long-term effects of low-dose bevacizumab on neurodevelopment and retinal structure.
Guevarra MCB, Eala MAB, Dee EC, Mercado GJV, Collantes ERA. Looking through the scope: retinoblastoma in the Philippines. Eye (Lond) 2022;
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Halawa OA, Kolli A, Oh G, Mitchell WG, Glynn RJ, Kim DH, Friedman DS, Zebardast N. Racial and Socioeconomic Differences in Eye Care Utilization among Medicare Beneficiaries with Glaucoma. Ophthalmology 2022;129(4):397-405.Abstract
PURPOSE: Evaluate differences in eye care utilization among patients with glaucoma by race and socioeconomic status (SES). DESIGN: Retrospective cohort study. PARTICIPANTS: Representative 5% sample of Medicare beneficiaries aged > 65 years with continuous part A/B enrollment between January 1, 2014, and July 1, 2014, at least 1 diagnosis code for glaucoma within that period, and a glaucoma diagnosis in the Chronic Conditions Warehouse before January 1, 2014. METHODS: The following race/ethnicity categories were defined in our cohort: non-Hispanic White, Black/African American, Hispanic, and Asian/Pacific Islander. Low SES was defined as having 2 or more enrollment-based low-income indicators (dual eligibility for Medicare/Medicaid, Part D limited income subsidies, and eligibility for Part A and B State buy-in). Negative binomial regression analyses were carried out to compare relative rate ratios (RRs) of eye care utilization among racial groups stratified by low and non-low SES. MAIN OUTCOME MEASURES: Measured from July 1, 2014, to December 31, 2016: eye examinations and eye care-related office visits; eye care-related inpatient and emergency department (ED) encounters; eye care-related nursing home and home-visit encounters; visual field and retinal nerve fiber OCT tests; glaucoma lasers and surgeries. RESULTS: Among 78 526 participants with glaucoma, mean age was 79.1 years (standard deviation, 7.9 years), 60.9% were female, 78.4% were non-Hispanic White, and 13.8% met enrollment-based criteria for low-SES. Compared with White beneficiaries, Blacks had lower counts of outpatient visits (RR, 0.92; 95% confidence interval [CI], 0.90-0.93), visual field (VF) tests (RR, 0.92; 95% CI, 0.90-0.94), but more inpatient/ED encounters (RR, 2.42; 95% CI, 1.55-3.78) and surgeries (RR, 1.14; 95% CI, 1.03-1.27). Hispanics had fewer outpatient visits (RR, 0.97; 95% CI, 0.95-0.98) and retinal nerve fiber layer (RNFL) OCT tests (RR, 0.89; 95% CI, 0.86-0.93), but more inpatient/ED encounters (RR, 2.32; 95% CI, 1.18-4.57) and selective laser trabeculoplasty (SLT) (RR, 1.25; 95% CI, 1.11-1.42) versus non-Hispanic Whites. In the non-low SES group, Black versus White disparities persisted in outpatient visits (RR, 0.93; 95% CI, 0.92-0.95), VF (RR, 0.96; 95% CI, 0.94-0.98), RNFL OCT (RR, 0.81; 95% CI, 0.78-0.83), and inpatient/ED encounters (RR, 2.57; 95% CI, 1.55-4.26). CONCLUSIONS: Disparities were found in eye care utilization among Black and Hispanic patients with glaucoma. These differences persisted among Blacks after stratification by SES, suggesting that systemic racism may be an independent driver in this population.
Hall NE, Chang EK, Samuel S, Gupta S, Klug E, Elze T, Lorch AC, Miller JW, Solá-Del Valle D. Risk factors for glaucoma drainage device revision or removal using the IRIS Registry. Am J Ophthalmol 2022;Abstract
PURPOSE: To elucidate risk factors for revision or removal of glaucoma drainage devices (GDD) in glaucoma patients in the United States. DESIGN: Retrospective cohort study. METHODS: IRIS® Registry (Intelligent Research in Sight) patients who underwent GDD insertion between 01/01/2013 and 12/31/2018 were included. Various demographic and clinical factors were collected. Kaplan-Meier (KM) survival plots, Cox proportional-hazard models utilizing Firth's Penalized Likelihood (CRFPL), and multivariate linear regression models were used. The main outcome measures were hazard ratios (HRs) and beta coefficient (β) estimates. RESULTS: 44,330 distinct patients underwent at least one GDD implantation, and 3,354 of these underwent subsequent GDD revision or removal surgery. With failure defined as GDD revision/removal, factors significantly associated with decreased failure included unknown race (HR=0.83; p=0.004) and unknown ethnicity (HR=0.68; p<0.001). Factors associated with increased risk of GDD revision/removal surgery included presence of chronic angle closure glaucoma (HR=1.32; p<0.001) and dry eye disease (HR=1.30; p=0.007). Additionally, factors associated with a decreased average time (in days) to GDD revision/removal included male sex (β=-25.96; p=0.044), unknown race (β=-55.28; p=0.013), and right-eye laterality (β=-38.67; p=0.026). Factors associated with an increased average time to GDD revision/removal included having a history of a past eye procedure (β=104.83; p<0.001) and being an active smoker (β=38.15; p=0.024). CONCLUSIONS: The size and scope of the IRIS Registry allows for detection of subtle associations between risk factors and GDD revision or removal surgery. Aforementioned demographic and clinical factors may all have an impact on GDD longevity and can inform the treatment options available for glaucoma patients.
Hallal R, Armstrong GW, Pineda R. Long-Term Outcomes of Big Bubble Deep Anterior Lamellar Keratoplasty in Mucopolysaccharidoses: A Retrospective Case Series and Review of the Literature. Cornea 2022;Abstract
PURPOSE: The purpose of this study was to report the long-term surgical and visual outcomes of patients with mucopolysaccharidoses (MPS) after big bubble deep anterior lamellar keratoplasty (BB-DALK). METHODS: This was a retrospective case series of patients with MPS who underwent BB-DALK at a single academic institution. All patients had corneal clouding secondary to MPS limiting visual acuity for which keratoplasty was indicated. Each patient was evaluated and underwent surgery by a single surgeon. Reported data included age at keratoplasty, sex, MPS type, best spectacle-corrected visual acuity, change in pachymetry, ocular comorbidities, surgical complications, and MPS-related medication use. RESULTS: Outcomes of 12 eyes from 7 patients with MPS type I (Hurler, Scheie, and Hurler-Scheie) are reported using the newest nomenclature. The mean follow-up was 5.58 years (range: 1-10 years). All cases underwent BB-DALK with a type 1 big bubble during the surgery. Two cases (16.6%) required rebubbling because of partial Descemet membrane detachment. One case was complicated by a suture abscess and required a penetrating keratoplasty. No episodes of rejection occurred. Statistically significant improvement in the best spectacle-corrected visual acuity (from a mean 0.85-0.33 logarithm of the minimum angle of resolution, P = logarithm of the minimum angle of resolution 0.0054) and pachymetry (mean reduction of -145.4 μm, P = 0.0018) was observed. CONCLUSIONS: BB-DALK seems to be an acceptable long-term surgical option in patients with MPS. Our findings suggest that this technique is reproducible and can achieve clear corneal grafts with good visual results on a long-term follow-up.
Huang JJ, Geduldig JE, Jacobs EB, Tai TYT, Ahmad S, Chadha N, Buxton DF, Vinod K, Wirostko BM, Kang JH, Wiggs JL, Ritch R, Pasquale LR. Head and neck region dermatological UV-related cancers are associated with exfoliation syndrome in a clinic-based population. Ophthalmol Glaucoma 2022;Abstract
OBJECTIVE: We assessed the relation between UV-associated dermatological carcinomas (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) and exfoliation syndrome with or without glaucoma (XFS/XFG). DESIGN: Case-control study. Subjects, participants, and controls:321 participants with XFS/XFG, primary open angle glaucoma (POAG), and control subjects (XFS/XFG = 98, POAG = 117, control = 106, ages 50-90) were recruited between 2019-2021. METHODS: Subjects were recruited for a cross-sectional survey assessing medical history, maximum known intraocular pressure, cup-to-disc ratio, Humphrey Visual Field 24-2 (HVF), propensity to tan or burn in early life, history of BCC and/or SCC and XFS/XFG diagnosis. We generated multivariable models adjusting for age, sex, medical history, eye color, hair color, and likeliness of tanning vs burning at a young age. MAIN OUTCOME MEASURES: History of diagnosed XFS/XFG. RESULTS: Any history of BCC/SCC in the head and neck region was associated with a 2-fold higher risk for having XFS/XFG versus having POAG or being a control subject (odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.04 - 3.89) in multivariable-adjusted analysis. Additionally, we observed a dose-response association where the chance of having XFS/XFG was higher by 67% per head and neck BCC/SCC occurrence (OR = 1.67, 95% CI = 1.09 - 2.56). When we excluded POAG participants, head and neck BCC/SCC was associated with 2.8-fold higher risk of XFS/XFG (OR = 2.80, 95% CI = 1.12 - 7.02) and each additional occurrence of head and neck BCC/SCC had a 2-fold higher risk for XFS/XFG (OR = 1.97, 95% CI = 1.09 - 3.58). The association between head and neck region BCC/SCC and POAG compared to control subjects was null (OR = 1.42, 95% CI = 0.58 - 3.48). When BCC/SCC located anywhere on the body was considered, there was a non-significant higher risk of XFS/XFG compared to having POAG or being a control subject (OR = 1.65, 95% CI = 0.88 - 3.09). CONCLUSIONS: Head and neck region BCC/SCCs are associated with a higher risk for having XFS/XFG. These findings support prior evidence that head and neck UV exposure may be a risk factor for XFS.
Huang YY, Hrycaj SM, Chan MP, Stagner AM, Patel RM, Bresler SC. PRAME Expression in Junctional Melanocytic Proliferations of the Conjunctiva: A Potential Biomarker for Primary Acquired Melanosis/Conjunctival Melanocytic Intraepithelial Lesions. Am J Dermatopathol 2022;Abstract
ABSTRACT: Conjunctival melanocytic proliferations are diagnostically challenging, often complicated by small specimen size, and are separated into 3 broad categories. The first group includes benign nevi and primary acquired melanosis (PAM) without atypia. The second group includes junctional melanocytic proliferations with a risk of progression to invasive melanoma (PAM with atypia). The last category is conjunctival melanoma, of which 65% of tumors arise in the setting of PAM with atypia. Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has been widely adopted to differentiate cutaneous nevi and melanoma. However, there are limited studies on its utility in the evaluation of conjunctival melanocytic proliferations with little data regarding its potential utility in stratifying PAM. Twenty-eight clinically annotated cases (14 PAM without atypia and 14 PAM with atypia) were retrospectively evaluated with PRAME/MART-1 duplex immunohistochemistry and were assigned the commonly used PRAME immunoreactivity score: 0 for no staining, 1+ for 1%-25% of cells positive, 2+ for 26%-50%, 3+ for 51%-75%, and 4+ for >75%. PAM without atypia showed low (0-3+) PRAME expression in 14 of 14 cases (100%). PAM with atypia showed strong and diffuse (4+) PRAME expression in 12 of 14 cases (86.7%). Seven of eight (87.5%) PAM with severe atypia, 4 of 4 PAM (100%) with moderate atypia, and 1 of 2 PAM (50%) with mild atypia showed 4+ PRAME expression. In addition, all 5 cases that recurred or progressed (all classified as PAM with atypia) showed 4+ PRAME expression. Although additional larger studies are needed, PRAME seems to be a useful adjunct in evaluating junctional melanocytic proliferations of the conjunctiva.
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Jacoba CMP, Ashraf M, Cavallerano JD, Tolson AM, Tolls D, Pellegrini E, Fleming A, Sun JK, Aiello LP, Silva PS. Association of Maximizing Visible Retinal Area by Manual Eyelid Lifting With Grading of Diabetic Retinopathy Severity and Detection of Predominantly Peripheral Lesions When Using Ultra-Widefield Imaging. JAMA Ophthalmol 2022;140(4):421-425.Abstract
Importance: Methods that increase visible retinal area (VRA; measured in millimeters squared) may improve identification of diabetic retinopathy (DR) lesions. Objective: To evaluate the association of dilation and manual eyelid lifting (MLL) with VRA on ultra-widefield imaging (UWFI) and the association of VRA with grading of DR severity and detection of predominantly peripheral lesions (PPLs). Design, Setting, and Participants: Retrospective, comparative case-control study at the Joslin Diabetes Center, Boston, Massachusetts. Nonmydriatic UWFI with MLL was acquired from a DR teleophthalmology program (Joslin Vision Network [JVN]). A second cohort of mydriatic UWFI was acquired at an academic retina practice (Beetham Eye Institute [BEI]) from November 6, 2017, to November 6, 2018, and with MLL thereafter until November 6, 2019. Fully automated algorithms determined VRA and hemorrhage and/or microaneurysm (HMA) counts. Predominantly peripheral lesions and HMAs were defined as present when at least 1 field had greater HMA number in the peripheral retina than within the corresponding Early Treatment Diabetic Retinopathy Study field. Participants included 3014 consecutive patients (5919 eyes) undergoing retinal imaging at JVN and BEI. Exposures: Dilation and MLL performed at the time of UWFI. Main Outcomes and Measures: Visible retinal area, DR severity, and presence of PPLs. Results: Of the 3014 participants, mean (SD) age was 56.1 (14.5) years, 1302 (43.2%) were female, 2450 (81.3%) were White, and mean (SD) diabetes duration was 15.9 (11.4) years. All images from 5919 eyes with UWFI were analyzed. Mean (SD) VRA was 665.1 (167.6) mm2 for all eyes (theoretical maximal VRA, 923.9 mm2), 550.8 (240.7) mm2 for nonmydriatic JVN with MLL (1418 eyes [24.0%]), 688.1 (119.9) mm2 for mydriatic BEI images (3650 eyes [61.7%]), and 757.0 (69.7) mm2 for mydriatic and MLL BEI images (851 eyes [14.4%]). Dilation increased VRA by 25% (P < .001) and MLL increased VRA an additional 10% (P < .001). Nonmydriatic MLL increased VRA by 11.0%. With MLL, HMA counts in UWFI fields increased by 41.7% (from 4.8 to 6.8; P < .001). Visible retinal area was moderately associated with increasing PPL-HMA overall and in each cohort (all, r = 0.33; BEI, r = 0.29; JVN, r = 0.36; P < .001). In JVN images, increasing VRA was associated with more PPL-HMA (quartile 1 [Q1], 23.7%; Q2, 45.8%; Q3, 60.6%; and Q4, 69.2%; P < .001). Conclusions and Relevance: Using fully automated VRA and HMA detection algorithms, pupillary dilation and eyelid lifting were shown to substantially increase VRA and PLL-HMA detection. Given the importance of HMA and PPL for determining risk of DR progression, these findings emphasize the importance of maximizing VRA for optimal risk assessment in clinical trials and teleophthalmology programs.
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Kim JE, Glassman AR, Josic K, Melia M, Aiello LP, Baker C, Eells JT, Jampol LM, Kern TS, Marcus D, Salehi-Had H, Shah SN, Martin DF, Stockdale CR, Sun JK, Sun JK. A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE). Ophthalmol Retina 2022;6(4):298-307.Abstract
PURPOSE: To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision. DESIGN: Phase 2 randomized clinical trial. PARTICIPANTS: Participants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the United States. METHODS: One eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months. MAIN OUTCOME MEASURES: Change in CST on spectral-domain OCT at 4 months. RESULTS: From April 2019 to February 2020, 135 adults were randomly assigned to either PBM (n = 69) or placebo (n = 66); median age was 62 years, 37% were women, and 82% were White. The median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes, with the mean difference (95% confidence interval [CI]) being -2 (-20 to 16) μm (P = 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90%) PBM eyes and 57 (86%) placebo eyes at 4 months (adjusted odds ratio [95% CI] = 1.30 (0.44-3.83); P = 0.63). VA decreased by a mean (SD) of -0.2 (5.5) letters and -0.6 (4.6) letters in the PBM and placebo groups, respectively (difference [95% CI] = 0.4 (-1.3 to 2.0) letters; P = 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious. CONCLUSIONS: PBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.
Kunkler AL, Patel NA, Russell JF, Fan KC, Al-Khersan H, Iyer PG, Acon D, Negron CI, Yannuzzi NA, Berrocal AM. Intraoperative OCT Angiography in Children with Incontinentia Pigmenti. Ophthalmol Retina 2022;6(4):330-332.

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