April 2022

Tam EK, Elhusseiny AM, Shah AS, Mantagos IS, VanderVeen DK. Etiology and outcomes of childhood glaucoma at a tertiary referral center. J AAPOS 2022;Abstract
PURPOSE: To describe the etiology, clinical features, and outcomes for a large contemporary cohort of children presenting with glaucoma at a tertiary referral center. METHODS: The medical records of patients presenting to Boston Children's Hospital from January 2014 to July 2019 with a diagnosis of childhood glaucoma were retrospectively reviewed. Data regarding etiology, treatment, and visual and anatomic outcomes were collected; visual acuity outcomes were analyzed by laterality and diagnosis categories, using the Childhood Glaucoma Research Network (CGRN) classifications. RESULTS: A total of 373 eyes of 246 patients (51% males) diagnosed with glaucoma before 18 years of age were identified. Mean follow-up was 7.04 ± 5.61 years; 137 cases were bilateral. The mean age at diagnosis was 4.55 ± 5.20 years. The most common diagnoses were glaucoma following cataract surgery (GFCS, 36.5%) and primary congenital glaucoma (PCG, 29.0%). Overall, 164 eyes (44.0%) underwent at least one glaucoma surgery. Intraocular pressure (IOP) was ≤21 mm Hg with or without glaucoma medications in 300 eyes (80.4%) at the last follow-up visit. Poor final best-corrected visual acuity (≤20/200) was found in 110 eyes; patients with poor final visual acuity tended to have poor visual acuity at presentation. The most common reason for poor vision was amblyopia. Uncontrolled IOP was an uncommon cause for vision loss. CONCLUSIONS: Childhood glaucoma can be challenging to manage, but poor vision usually results from amblyopia or presence of other ocular abnormalities or syndromes rather than glaucomatous optic neuropathy.
Lin LY, Reshef ER, Lansberg MP, Barshak MB, Chwalisz BK, Holbrook EH, Wolkow N. Posterior Ischemic Optic Neuropathy in the Setting of Cocaine-Induced Orbital and Sinonasal Inflammation. Ophthalmic Plast Reconstr Surg 2022;Abstract
Intranasal cocaine abuse can lead to significant sinus and orbital complications, including optic neuropathy. A 46-year-old man with a history of recurrent cocaine-induced sino-orbital inflammation and infection with bony destruction presented with acute, painless, vision loss. Examination revealed no light perception vision. MRI of the orbits demonstrated new restricted diffusion of the right optic nerve on diffusion-weighted imaging and apparent diffusion coefficient sequences, consistent with posterior ischemic optic neuropathy. This is the first among cases of cocaine-induced optic neuropathy in the literature to illustrate ischemic changes on MRI in the optic nerve, highlighting the utility of diffusion-weighted imaging/apparent diffusion coefficient sequences when optic neuropathy is suspected and further suggesting an underlying ischemic etiology in similar cases.
Xie L, Cen L-P, Li Y, Gilbert H-Y, Strelko O, Berlinicke C, Stavarache MA, Ma M, Wang Y, Cui Q, Kaplitt MG, Zack DJ, Benowitz LI, Yin Y. Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells' response to Pten deletion. Proc Natl Acad Sci U S A 2022;119(15):e2113751119.Abstract
SignificanceThe optic nerve conveys information from retinal ganglion cells (RGCs) to visual processing areas of the brain. Although this pathway normally cannot regenerate when injured nor in degenerative diseases such as glaucoma, this failure can be partially reversed by eliciting a controlled immune reaction in the eye. We show here that the chemokine SDF1 (stromal cell-derived factor 1) is an important contributor to this phenomenon. SDF1 is produced by infiltrative monocytes and acts through its cognate receptor to enhance RGC survival, promote optic nerve regeneration, and sensitize subtypes of RGCs that normally fail to respond to a complementary treatment to exhibit robust, long-distance regeneration. These findings establish SDF1 as an important therapeutic candidate for repairing the injured optic nerve.
Okumura Y, Inomata T, Midorikawa-Inomata A, Sung J, Fujio K, Akasaki Y, Nakamura M, Iwagami M, Fujimoto K, Eguchi A, Miura M, Nagino K, Hirosawa K, Huang T, Kuwahara M, Dana R, Murakami A. DryEyeRhythm: A reliable and valid smartphone application for the diagnosis assistance of dry eye. Ocul Surf 2022;Abstract
PURPOSE: Undiagnosed or inadequately treated dry eye disease (DED) decreases the quality of life. We aimed to investigate the reliability, validity, and feasibility of the DryEyeRhythm smartphone application (app) for the diagnosis assistance of DED. METHODS: This prospective, cross-sectional, observational, single-center study recruited 82 participants (42 with DED) aged ≥20 years (July 2020-May 2021). Patients with a history of eyelid disorder, ptosis, mental disease, Parkinson's disease, or any other disease affecting blinking were excluded. Participants underwent DED examinations, including the Japanese version of the Ocular Surface Disease Index (J-OSDI) and maximum blink interval (MBI). We analyzed their app-based J-OSDI and MBI results. Internal consistency reliability and concurrent validity were evaluated using Cronbach's alpha coefficients and Pearson's test, respectively. The discriminant validity of the app-based DED diagnosis was assessed by comparing the results of the clinical-based J-OSDI and MBI. The app feasibility and screening performance were evaluated using the precision rate and receiver operating characteristic curve analysis. RESULTS: The app-based J-OSDI showed good internal consistency (Cronbach's α = 0.874). The app-based J-OSDI and MBI were positively correlated with their clinical-based counterparts (r = 0.891 and r = 0.329, respectively). Discriminant validity of the app-based J-OSDI and MBI yielded significantly higher total scores for the DED cohort (8.6 ± 9.3 vs. 28.4 ± 14.9, P < 0.001; 19.0 ± 11.1 vs. 13.2 ± 9.3, P < 0.001). The app's positive and negative predictive values were 91.3% and 69.1%, respectively. The area under the curve (95% confidence interval) was 0.910 (0.846-0.973) with concurrent use of the app-based J-OSDI and MBI. CONCLUSIONS: DryEyeRhythm app is a novel, non-invasive, reliable, and valid instrument for assessing DED.
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.
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.
Kwan J, Ahmed H, Ponsetto MK, Succar T, Chodosh J, Saeed HN. Relationship between Atopic Disease and Acute Ocular and Systemic Outcomes in Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. Ocul Immunol Inflamm 2022;:1-5.Abstract
OBJECTIVE: To describe the relationship between history of atopic disease on systemic and ocular manifestations of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). METHODS: Retrospective chart review of patients with SJS/TEN patients. Those with and without prior atopic diagnosis were compared. RESULTS: In total, 200 patients with SJS/TEN were identified. A total of 23 patients also had an atopic diagnosis. Four, 10, and 18 had atopic dermatitis, allergic rhinitis, and asthma respectively. Acute ocular severity was significantly worse in the atopic cohort. No significant differences in overall systemic severity of SJS or mortality were found between the atopic and non-atopic cohorts. Compared to our hospital system's general population, prevalence of an atopic diagnosis was significantly higher in those with SJS/TEN. CONCLUSION: Patients with a history of an atopic diagnosis appear to have more significant acute ocular involvement during their SJS/TEN hospitalization. Atopic conditions appear to occur more frequently in the SJS/TEN population compared to the general population.
Ou J, Lan W, Wu X, Zhao T, Duan B, Yang P, Ren Y, Quan L, Zhao W, Seto D, Chodosh J, Luo Z, Wu J, Zhang Q. Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events. Signal Transduct Target Ther 2022;7(1):138.Abstract
The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, 18 core mutations of BA.1 (frequency >99%) and 27 core mutations of BA.2 (nine more than BA.1) were identified, of which 15 are specific to Omicron. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations in BA.1 than BA.2, and BA.1 is phylogenetically closer to Alpha than other variants. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1. Most notably, multiple characteristic amino acid mutations in the Delta spike protein have been also identified in the "Deltacron"-like Omicron Variants isolated since November 11, 2021 in South Africa, which implies the recombination events occurring between the Omicron and Delta variants. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.
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.
Ofuji Y, Katada Y, Tomita Y, Nagai N, Sonobe H, Watanabe K, Shinoda H, Ozawa Y, Negishi K, Tsubota K, Kurihara T. Non-Perfusion Area Index for Prognostic Prediction in Diabetic Retinopathy. Life (Basel) 2022;12(4)Abstract
Fundus fluorescent angiography is a standard examination in Japan that can directly visualize the circulatory failure in diabetic retinopathy but is not used in Western countries. In this study, we examine the relationship between the non-perfusion area in fundus fluorescent angiography and the progression of diabetic retinopathy. We evaluated 22 eyes between 22 patients who had their first fundus fluorescent angiography during a clinical episode at Keio University Hospital from January 2012 to May 2015, were diagnosed as having preproliferative diabetic retinopathy, and could be followed for at least three years. The non-perfusion area index (%) in nine segmented fundi in the initial fundus fluorescent angiography was calculated, and the progression to proliferative diabetic retinopathy over three years was evaluated. Three out of the 22 eyes (13.6%) developed proliferative diabetic retinopathy over three years. The non-perfusion area index for the initial fundus fluorescent angiography was significantly associated with progression to proliferative diabetic retinopathy. The non-perfusion area index in the posterior pole was most strongly correlated with the progression to proliferative diabetic retinopathy. Thus, the non-perfusion area index in the posterior pole among those with preproliferative diabetic retinopathy may predict the progression to proliferative diabetic retinopathy in the subsequent three years.
Weakley DR, Nizam A, VanderVeen DK, Wilson EM, Kruger S, Lambert SR, Lambert SR. Myopic Shift at 10 Years Follow-up in the Infant Aphakia Treatment Study. Ophthalmology 2022;Abstract
We studied the myopic shift and anisometropia at 10.6 (+/-0.3) years of age in the Infant Aphakia Treatment Study. We found myopic shift continues in the operated eye from 5-10.5 years at a lower rate than that prior to age five years while anisometropia increases proportionally. The Infant Aphakia Treatment Study (IATS) is a randomized clinical trial initially designed to compare outcomes in infants under seven months of age who underwent primary implantation of an intraocular lens (IOL) versus being left aphakic and receiving a contact lens correction following cataract surgery in infancy.1 Patients were enrolled from 2004 through 2009 with the last 10-year follow-up exam completed in 2019. The study design was approved by the institutional review boards of the 12 participating sites and followed the tenets of the Declaration of Helsinki. The off-label use of the AcrySof SN60AT and MA60AC IOLs (Alcon Laboratories, Fort Worth Tx.) was covered under the United States Food and Drug Administration investigational device exemption. The trial is registered at www.ClinicalTrials.gov (identifier, NCT00212134).

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