Amniotic membrane transplantation as part of a multimodal management approach to Streptococcus pyogenes necrotizing keratoconjunctivitis.

Streptococcus pyogenes (group A beta-hemolytic Streptococcus, GABHS) causes a range of human infections, including necrotizing fasciitis and toxic shock syndrome, because it produces exotoxins that damage host cells, facilitate immune evasion, and serve as T cell superantigens. GABHS conjunctivitis is rare. We report a case of membranous conjunctivitis in a 3-year-old child who was treated with a combination of targeted bactericidal antimicrobials, toxin-synthesis inhibition, and amniotic membrane transplantation.

Surgical management of superior oblique palsy with coexisting exotropia.

PURPOSE: To analyze the surgical results of patients treated for superior oblique palsy with coexisting exotropia. METHODS: The medical records of patients with superior oblique palsy and exotropia who underwent inferior oblique weakening and simultaneous lateral rectus recession by a single surgeon from 1996 to 2022 were reviewed retrospectively. Demographics, pre- and postoperative vertical and horizontal deviation, and presence of diplopia were recorded. Surgical success was defined as horizontal deviation <10Δ and vertical deviation ≤4Δ without overcorrection or diplopia. The decision to operate for the horizontal deviation was made based on fusion in free space when the vertical deviation was offset with a prism. RESULTS: A total of 27 patients were included. Mean age was 26.1 ± 22 years (range, 26 months to 78 years). Preoperatively, mean vertical deviation was 15.2Δ ± 7.5Δ (range, 4Δ-30Δ); mean exodeviation, 17Δ ± 5.5Δ (range, 10Δ-35Δ). Of the 27 patients, 25 underwent unilateral and 2 underwent bilateral lateral rectus recession, according to the magnitude of the horizontal deviation. Mean follow-up was 3 ± 3.8 months (range, 2 weeks to 17 months). Postoperative mean vertical alignment was 3.0 ± 5.9, and horizontal alignment was 3.4Δ ± 5.2Δ (esotropia of 7Δ to exotropia of 12Δ; P < 0.0001). Nineteen patients (70%) had a successful result; 2 patients had residual exotropia of >10Δ, 2 had vertical overcorrection (range, 3Δ-4Δ), and 6 had residual vertical deviation ≥4Δ (range, 5Δ-20Δ). None had secondary esotropia >10Δ. Horizontal deviation was corrected successfully with no consecutive esotropia in 25 patients. CONCLUSIONS: In our study cohort, patients with superior oblique palsy and exotropia in whom fusion required both horizontal and vertical prism correction had a high likelihood of successful horizontal alignment after lateral rectus weakening in combination with inferior oblique surgery.

Outcomes of inferonasal glaucoma drainage device surgery in the management of childhood glaucoma.

PURPOSE: To evaluate indications and postoperative outcomes of inferonasal Ahmed and Baerveldt glaucoma drainage devices (GDDs) in pediatric glaucoma. METHODS: This retrospective study included patients ≤18 years of age at inferonasal GDD placement, from June 2013 to September 2021. Demographic information, indications, and outcomes were recorded. Successful eyes had intraocular pressure (IOP) ≥5 and ≤21 mm Hg or (in severe cases, where entry IOP was ≤21 mm Hg) 20% below preoperative values without additional IOP-lowering surgery or vision-threatening complications. RESULTS: A total of 68 eyes of 52 patients were included. Mean age was 9.8 ± 5.8 years. Most common diagnoses included primary congenital glaucoma (n = 28 eyes [41%]) and glaucoma following cataract surgery (n = 12 eyes [18%]). Success rates by Kaplan-Meier survival analysis (95% CI) at 1, 2, 3, and 5 years were 62.2% (49.4-72.7), 49.0% (36.3-60.6), 36.8% (24.0-49.8), and 31.9% (18.5-44.5), respectively. Surgical failure was associated with Ahmed (vs Baerveldt) GDD (HR = 3.2; P = 0.002) and inferonasal site as initial (vs subsequent) GDD received (HR = 2.2; P = 0.048). Twenty-five eyes (36.7%) had at least one complication. Although vision-threatening complications were uncommon (n = 2 eyes [3%]), less severe complications were relatively common and included new/worsened strabismus (n = 9 patients [17%]), corneal edema (n = 6 eyes [9%]), lens opacities (n = 4 [6%]), tube or patch graft exposure (n = 3 [4%]), tube blockage (n = 2 eyes [3%]), and other (n = 8 eyes [12%]). CONCLUSIONS: In this study cohort, inferonasal GDDs for childhood glaucoma had modest success, with frequent though rarely vision-threatening complications.

Rebound tonometry by iCare 200 (IC200): comparison with Tono-Pen in the operating room and Goldmann applanation in the clinic.

BACKGROUND: Tonometry guides decision making in children with known or suspected glaucoma. The iCare IC200 is a recently FDA-approved rebound tonometer that can measure intraocular pressure (IOP) in both supine and upright patients. The purpose of this study was to evaluate this new tonometer against more commonly used standard instruments: Tono-Pen in the operating room (OR arm) and Goldmann applanation in the clinic (clinic arm). METHODS: The OR arm included sequential children undergoing general anesthesia. The clinic arm included cooperative children seen in clinic. IOP was measured twice (right eye then left eye, repeat) with IC200 and either Tono-Pen (OR arm) or Goldmann (clinic arm). RESULTS: A total of 99 children were included: 75 for the OR arm and 24 for the clinic arm. There was a strong correlation between the IOP measured by IC200 and each device (R2 = 0.81 for Tono-Pen; R2 = 0.78 for Goldmann). In the OR arm, the overall mean IOP difference (ΔIOP [Tono-Pen - IC200]) was -1.6 mm Hg. For eyes with corneal edema (n = 12), ΔIOP ranged from -8 to 15 mm Hg. At IOP >20 mm Hg, mean ΔIOP was -3.7 mm Hg. In the clinic arm, the mean ΔIOP (ΔIOP [Goldmann - IC200]) was -1.2 mm Hg. CONCLUSIONS: In eyes of children under general anesthesia with IOP <20 mm Hg without corneal edema, IC200 and Tono-Pen correlated well. In cooperative clinic patients, Goldmann and IC200 correlated well over the range of IOP studied.

Medial Rectus Advancement for Secondary Exotropia.

PURPOSE: To determine the preoperative characteristics and surgical results after medial rectus advancement in patients with secondary exotropia. DESIGN: Retrospective, interventional case series. METHODS: Setting: Tertiary Care University Medical Center. PatientPopulation: 221 patients with a diagnosis of secondary exotropia who underwent medial rectus advancement surgery by a single surgeon. OBSERVATION: Preoperative demographics, exodeviation and motility, intraoperative findings, and postoperative results were recorded. MainOutcomeMeasure: Success of surgery, defined as Esotropia <15 prism diopters (pd) at postoperative week 1, or any deviation of <8 pd at postoperative month 2 (POM2). RESULTS: A total of 98 patients underwent unilateral medial rectus advancement (UMRadv), 89 underwent UMRadv with lateral rectus recession (LRc), and 34 underwent bilateral medial rectus advancement (BMRadv). POM2 success rates were 66.7% in UMRadv patients, 62.1% in UMRadv + LRc, and 56% in BMRadv. A total of 117 patients had preoperative adduction deficits, which were significantly associated with the finding of an intraoperative stretched scar (P < .001). Larger preoperative duction deficits were associated with larger stretched scars (P < .001). At POM2, the mean effect of surgery (pd of correction/mm) was 2.3 ± 1.4 pd/mm for UMRadv, 2.5 ± 0.8 pd/mm for UMRadv + LRc, and 2.8 ± 1.1 pd/mm for BMRadv. Patients with a stretched scar had significantly less correction per millimeter (2.2 ± 1.2 pd/mm) compared with those without (2.6 ± 1.2 pd/mm, P < .001). A total of 38.6% of patients experienced exodrift greater than 10 pd. Exodrift was significantly larger in the BMRadv group (P < .005). DISCUSSION: These results provide guidance for surgical correction based on preoperative deviation and ductions. Adduction deficits indicate a stretched scar, which must be treated with resection and advancement of the medial rectus. A larger amount of surgery is needed in patients with a stretched scar. Exodrift is common, and therefore aiming for approximately 10 pd of overcorrection at postoperative week 1 can improve final outcomes. CONCLUSION: Medial rectus advancement results in successful surgical results at POM2 for secondary exotropia.

Surgical management of large bilateral epibulbar dermoids with autologous oral mucous membrane transplantation.

PURPOSE: To report the surgical management of extensive epibulbar dermoids with autologous oral mucous membrane transplantation. OBSERVATIONS: While rare, extensive dermoids that encroach upon the visual axis carry a poor prognosis. We report the case of a 7-week old premature male infant who presented with large bilateral epibulbar dermoids obscuring the visual axis. He was treated first with sequential bilateral optical iridectomies under the clearest corneal areas, followed several months later by sequential dermoid excision and amniotic membrane transplantation in each eye. He subsequently underwent autologous "simple" oral mucosal epithelial transplantation (SOMET) as well as strabismus surgery. Conclusions and Importance: Here we present the first case, to the best of our knowledge, of the use of SOMET in managing post-operative pseudopterygium following dermoid excision. To our knowledge it is the also the first application of this technique in a young pediatric patient. A good clinical outcome may be achieved with SOMET, which may offer a minimally invasive alternative to other traditional modalities.

Prevalence of Ocular Pathology on Initial Screening and Incidence of New Findings on Follow-up Examinations in Children With Trisomy 21.

PURPOSE: Various ophthalmologic findings have been associated with trisomy 21. However, prior studies on this topic are limited by their sample size and the lack of follow-up regarding the incidence of new pathology after an initially normal examination. We determined whether children who have a normal first examination need to have formal reevaluation by an ophthalmologist. DESIGN: Retrospective cohort study. METHODS: Records were reviewed for 689 patients with trisomy 21 evaluated at Vanderbilt Eye Institute between 2012 and 2017. Ocular and refractive abnormalities present on initial screening were recorded and follow-up data were reviewed to determine if new abnormalities developed at subsequent visits. RESULTS: Of the 689 patients, 410 (59.5%) had a significant finding on their first examination. The most common abnormalities seen on initial screening examination were strabismus, significant refractive error, and eyelid abnormalities (including ectropion and accessory puncta). Of the 279 initially normal patients, 179 had at least 1 follow-up visit at a mean follow-up interval of 21.6 months (average age 3.7 years). At the first follow-up visit, 129 remained normal, while 50 had a new abnormality, most commonly significant refractive error and strabismus. On second follow-up visit, at a mean follow-up interval of 12 months (average age 4.8 years), 63% remained normal. CONCLUSIONS: Ocular pathology occurs in trisomy 21 at a much higher prevalence than the general population; thus these children initially should have a comprehensive eye examination. Although the development of new ocular pathology in a child with trisomy 21 and a previously normal examination is not unusual, most of these new abnormalities are detectable with automated vision screening techniques or direct visual inspection of the eyes and ocular adnexa; thus once a child has a normal examination, a formal vision screening could replace a formal ophthalmologic examination.

Short-term Optic Disc Cupping Reversal in a Patient With Mild Juvenile Open-angle Glaucoma Due to Early Idiopathic Intracranial Hypertension.

PURPOSE: The purpose of this study was to report a case of optic disc cupping reversal in an adult without significant intraocular pressure-lowering treatment. PATIENT: A 20-year-old female with a history of mild juvenile open-angle glaucoma who developed subjective blurred vision and a decrease in cupping of her optic discs. RESULTS: Dilated examination demonstrated decreased cup-to-disc ratios in both eyes with a slight blurring of the disc margin in the right eye. The appearance of both optic discs returned to baseline after weight loss therapy. CONCLUSIONS: An unexplained reduction of optic nerve cup-to-disc ratio should prompt a workup for other etiologies, such as increased intracranial pressure. Baseline photographs not subjected to computerized scan obsolescence are extremely useful in monitoring the long-term appearance of asymmetric optic discs as an adjunct to the clinical examination.

The Carnitine Shuttle Pathway is Altered in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: To identify metabolites and metabolic pathways altered in neovascular age-related macular degeneration (NVAMD). Methods: We performed metabolomics analysis using high-resolution C18 liquid chromatography-mass spectrometry on plasma samples from 100 NVAMD patients and 192 controls. Data for mass/charge ratio ranging from 85 to 850 were captured, and metabolic features were extracted using xMSanalyzer. Nested feature selection was used to identify metabolites that discriminated between NVAMD patients and controls. Pathway analysis was performed with Mummichog 2.0. Hierarchical clustering was used to examine the relationship between the discriminating metabolites and NVAMD patients and controls. Results: Of the 10,917 metabolic features analyzed, a set of 159 was identified that distinguished NVAMD patients from controls (area under the curve of 0.83). Of these features, 39 were annotated with confidence and included multiple carnitine metabolites. Pathway analysis revealed that the carnitine shuttle pathway was significantly altered in NVAMD patients (P = 0.0001). Tandem mass spectrometry confirmed the molecular identity of five carnitine shuttle pathway acylcarnitine intermediates that were increased in NVAMD patients. Hierarchical cluster analysis revealed that 51% of the NVAMD patients had similar metabolic profiles, whereas the remaining 49% displayed greater variability in their metabolic profiles. Conclusions: Multiple long-chain acylcarnitines that are part of the carnitine shuttle pathway were significantly increased in NVAMD patients compared to controls, suggesting that fatty acid metabolism may be involved in NVAMD pathophysiology. Cluster analysis suggested that clinically indistinguishable NVAMD patients can be separated into distinct subgroups based on metabolic profiles.

Mitochondrial Haplogroups Modify the Effect of Diabetes Duration and HbA1c on Proliferative Diabetic Retinopathy Risk in Patients With Type 2 Diabetes.

Purpose: We previously demonstrated an association between European mitochondrial haplogroups and proliferative diabetic retinopathy (PDR). The purpose of this study was to determine how the relationship between these haplogroups and both diabetes duration and hyperglycemia, two major risk factors for diabetic retinopathy (DR), affect PDR prevalence. Methods: Our population consisted of patients with type 2 diabetes with (n = 377) and without (n = 480) DR. A Kruskal-Wallis test was used to compare diabetes duration and hemoglobin A1c (HbA1c) among mitochondrial haplogroups. Logistic regressions were performed to investigate diabetes duration and HbA1c as risk factors for PDR in the context of European mitochondrial haplogroups. Results: Neither diabetes duration nor HbA1c differed among mitochondrial haplogroups. Among DR patients from haplogroup H, longer diabetes duration and increasing HbA1c were significant risk factors for PDR (P = 0.0001 and P = 0.011, respectively). Neither diabetes duration nor HbA1c was a significant risk factor for PDR in DR patients from haplogroup UK. Conclusions: European mitochondrial haplogroups modify the effects of diabetes duration and HbA1c on PDR risk in patients with type 2 diabetes. In our patient population, longer diabetes duration and higher HbA1c increased PDR risk in patients from haplogroup H, but did not affect PDR risk in patients from haplogroup UK. This relationship has not been previously demonstrated and may explain, in part, why some patients with nonproliferative DR develop PDR and others do not, despite similar diabetes duration and glycemic control.

Eye Care Disparities and Health-Related Consequences in Elderly Patients with Age-Related Eye Disease.

The elderly population in the United States (age 65 and older) is growing rapidly, estimated by the U.S. Census Department to reach 83.7 million by 2050.(1) Visual impairment increases with age among all racial and ethnic groups.(2) In the elderly, the most common culprits for vision loss are cataract, glaucoma, and age-related macular degeneration (AMD).(2) In the developed world, vision loss from cataract has been dramatically reduced by increased access to cataract surgery. However, AMD and glaucoma lead to irreversible vision loss without early diagnosis and intervention. In the U.S., cases of AMD are expected to double by 2050, reaching 17.8 million among patients age 50 or older.(3) Similarly, cases of glaucoma are expected to reach 5.5 million by 2050, an increase of over 90% from 2014.(3) The visually impaired elderly face disparities in access to eye care, and subsequent general medical and psychosocial complications.

Circulating Autoantibodies in Age-Related Macular Degeneration Recognize Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation, and Protection from Oxidative Stress and Apoptosis.

BACKGROUND: We investigated sera from elderly subjects with and without age-related macular degeneration (AMD) for presence of autoantibodies (AAbs) against human macular antigens and characterized their identity. METHODS: Sera were collected from participants in the Age-Related Maculopathy Ancillary (ARMA) Study, a cross-sectional investigation ancillary to the Health ABC Study, enriched with participants from the general population. The resulting sample (mean age: 79.2±3.9 years old) included subjects with early to advanced AMD (n = 131) and controls (n = 231). Sera were tested by Western blots for immunoreactive bands against human donor macular tissue homogenates. Immunoreactive bands were identified and graded, and odds ratios (OR) calculated. Based on these findings, sera were immunoprecipitated, and subjected to 2D gel electrophoresis (GE). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the targets recognized by circulating AAbs seen on 2D-GE, followed by ELISAs with recombinant proteins to confirm LC-MS/MS results, and quantify autoreactivities. RESULTS: In AMD, 11 immunoreactive bands were significantly more frequent and 13 were significantly stronger than in controls. Nine of the more frequent bands also showed stronger reactivity. OR estimates ranged between 4.06 and 1.93, and all clearly excluded the null value. Following immunoprecipitation, 2D-GE and LC-MS/MS, five of the possible autoreactivity targets were conclusively identified: two members of the heat shock protein 70 (HSP70) family, HSPA8 and HSPA9; another member of the HSP family, HSPB4, also known as alpha-crystallin A chain (CRYAA); Annexin A5 (ANXA5); and Protein S100-A9, also known as calgranulin B that, when complexed with S100A8, forms calprotectin. ELISA testing with recombinant proteins confirmed, on average, significantly higher reactivities against all targets in AMD samples compared to controls. CONCLUSIONS: Consistent with other evidence supporting the role of inflammation and the immune system in AMD pathogenesis, AAbs were identified in AMD sera, including early-stage disease. Identified targets may be mechanistically linked to AMD pathogenesis because the identified proteins are implicated in autophagy, immunomodulation, and protection from oxidative stress and apoptosis. In particular, a role in autophagy activation is shared by all five autoantigens, raising the possibility that the detected AAbs may play a role in AMD via autophagy compromise and downstream activation of the inflammasome. Thus, we propose that the detected AAbs provide further insight into AMD pathogenesis and have the potential to contribute to disease biogenesis and progression.

Metabolome-Wide Association Study of Primary Open Angle Glaucoma.

PURPOSE: To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics. METHODS: We used ultra-high resolution mass spectrometry with C18 liquid chromatography for metabolomic analysis on frozen plasma samples from 72 POAG patients and 72 controls. Metabolome-wide Spearman correlation was performed to select differentially expressed metabolites (DEM) correlated with POAG. We corrected P values for multiple testing using Benjamini and Hochberg false discovery rate (FDR). Hierarchical cluster analysis (HCA) was used to depict the relationship between participants and DEM. Differentially expressed metabolites were matched to the METLIN metabolomics database; both DEM and metabolites significantly correlating with DEM were analyzed using MetaboAnalyst to identify metabolic pathways altered in POAG. RESULTS: Of the 2440 m/z (mass/charge) features recovered after filtering, 41 differed between POAG cases and controls at FDR = 0.05. Hierarchical cluster analysis revealed these DEM to associate into eight clusters; three of these clusters contained the majority of the DEM and included palmitoylcarnitine, hydroxyergocalciferol, and high-resolution METLIN matches to sphingolipids, other vitamin D-related metabolites, and terpenes. MetaboAnalyst also indicated likely alteration in steroid biosynthesis pathways. CONCLUSIONS: Global ultrahigh resolution metabolomics emphasized the importance of altered lipid metabolism in POAG. The results suggest specific metabolic processes, such as those involving palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors, may contribute to POAG status and merit more detailed study with targeted methods.

Discharge instructions for youth sports-related concussions in the emergency department, 2004 to 2012.

OBJECTIVE: To evaluate the effect of the Centers for Disease Control and Prevention (CDC) Heads-Up concussion campaign on appropriateness of discharge instructions for youth sports-related concussion (SRC) patients presenting to a pediatric emergency department (ED). DESIGN: Retrospective cohort study. SETTING: Pediatric ED. PATIENTS: Children up to 18 years. ASSESSMENT OF RISK FACTORS: A retrospective chart review was conducted on patients evaluated from 2004 to 2012. Patients were selected by ICD-9 code for having a concussion during a sporting activity. MAIN OUTCOME MEASURES: Discharge instructions were reviewed for recommendations for cognitive rest, physical rest, primary care physician follow-up, and referral to a concussion specialist or center. RESULTS: There were 497 youth SRCs from 392 908 total ED visits. Overall, only 66% had appropriate discharge recommendations. This improved to 75% after 2010, which was not statistically significant (odds ratio = 1.02, P = 0.179). Only 4% of patients received a recommendation of cognitive rest, which only increased to 12% of the patients seen after 2010. Finally, referrals to a sports concussion specialist or center dramatically increased from an average of 8% to 43% after 2010. CONCLUSIONS: Even with the CDC Heads-Up campaign on concussion education, there is still need to improve appropriateness of discharge instructions for youth SRCs. There have been dramatic increases in referrals to sports concussion specialists and centers after 2010.

Retinal phenotypes in patients homozygous for the G1961E mutation in the ABCA4 gene.

PURPOSE: We evaluated the pathogenicity of the G1961E mutation in the ABCA4 gene, and present the range of retinal phenotypes associated with this mutation in homozygosity in a patient cohort with ABCA4-associated phenotypes. METHODS: Patients were enrolled from the ABCA4 disease database at Columbia University or by inquiry from collaborating physicians. Only patients homozygous for the G1961E mutation were enrolled. The entire ABCA4 gene open reading frame, including all exons and flanking intronic sequences, was sequenced in all patients. Phenotype data were obtained from clinical history and examination, fundus photography, infrared imaging, fundus autofluorescence, fluorescein angiography, and spectral domain-optical coherence tomography. Additional functional data were obtained using the full-field electroretinogram, and static or kinetic perimetry. RESULTS: We evaluated 12 patients homozygous for the G1961E mutation. All patients had evidence of retinal pathology consistent with the range of phenotypes observed in ABCA4 disease. The latest age of onset was recorded at 64 years, in a patient diagnosed initially with age-related macular degeneration (AMD). Of 6 patients in whom severe structural (with/without functional) fundus changes were detected, 5 had additional, heterozygous or homozygous, variants detected in the ABCA4 gene. CONCLUSIONS: Homozygous G1961E mutation in ABCA4 results in a range of retinal pathology. The phenotype usually is at the milder end of the disease spectrum, with severe phenotypes linked to the presence of additional ABCA4 variants. Our report also highlights that milder, late-onset Stargardt disease may be confused with AMD.