Publications

2022

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is an important etiology of neurologic morbidity and specifically, atypical, and relapsing optic neuritis. This review summarizes acute treatment and long-term prevention approaches in MOGAD. EVIDENCE ACQUISITION: PubMed and Google Scholar databases were manually searched and reviewed. RESULTS: We review the evidence base for acute treatment of MOGAD with corticosteroids and adjunct therapies, such as intravenous immunoglobulin (IVIg) and plasma exchange. We discuss the utility of prolonged corticosteroid tapering after the acute attack. We then summarize the commonly used disease-modifying treatments for relapsing MOGAD, including chronic low-dose corticosteroids, classic antirheumatic immune suppressants, biologic agents, and IVIg. CONCLUSIONS: While acute MOGAD attacks are usually treated with high-dose IV corticosteroids, longer oral corticosteroid tapers may prevent rapid relapse. Multiple long-term treatment strategies are being employed in recurrent MOGAD, with IVIg is emerging as probably the most effective therapy.
Madjedi K, Stuart K, Chua S, Luben R, Warwick A, Pasquale L, Kang J, Wiggs J, Lentjes MA, Aschard H, Sattar N, Foster P, Khawaja A, Consortium MRFGCUBEV. The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts. Ophthalmology. 2022;129(9):986–996.
PURPOSE: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). DESIGN: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. PARTICIPANTS: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. METHODS: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). MAIN OUTCOME MEASURES: Corneal-compensated IOP. RESULTS: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06-0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08-0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05-0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07-0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03-0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06-0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (-0.05 mmHg; 95% CI, -0.08 to -0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). CONCLUSIONS: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.
Adomfeh J, Jastrzembski B, Oke I. Association of Race, Ethnicity, and Socioeconomic Status With Visual Impairment in Adolescent Children in the US. JAMA Ophthalmol. 2022;140(10):1006–1010.
Importance: Although racial, ethnic, and socioeconomic disparities in visual impairment have been described in adults, few studies have focused on the adolescent population, which may provide insight into the emergence of vision health inequities. Objective: To describe visual health disparities among adolescent children in the US. Design, Setting, and Participants: This was a cross-sectional study of adolescents from the 2005 to 2008 National Health and Nutrition Examination Survey. Participants were aged 12 to 18 years with a completed visual function questionnaire and eye examination. Data analyses were conducted from January 19 to July 20, 2022. Main Outcomes and Measures: Outcomes included subjective (self-reported poor vision) and objective (visual acuity worse than 20/40 in the better-seeing eye) measures of visual function. Multivariable logistic and linear regression analyses were conducted to examine the association between the sociodemographic risk factors and each outcome, adjusting for age, sex, and other covariates. Results: The 2833 included participants (mean [SD] age, 15.5 [2.0] years; 1407 female participants [49%]) represent a survey-weighted 57 million US adolescent children, of whom 14% were non-Hispanic Black participants (876), 11% were Mexican American participants (828), 63% were non-Hispanic White participants (816), and 11% were other race and ethnicity (313). A total of 5% of participants (266) were not US citizens, and 19% (773) had a family income below the poverty threshold. There were increased odds of self-reported poor vision among Black (odds ratio [OR], 2.85; 95% CI, 2.00-4.05; P < .001), Mexican American (OR, 2.83; 95% CI, 1.70-4.73; P < .001), and low-income (OR, 2.44; 95% CI, 1.63-3.65; P < .001) adolescent children. Similarly, there were increased odds of visual acuity worse than 20/40 in the better-seeing eye among Black (OR, 2.13; 95% CI, 1.41-3.24; P = .001), Mexican American (OR, 2.13; 95% CI, 1.39-3.26; P = .001), and non-US citizen (OR, 1.96; 95% CI, 1.10-3.49; P = .02) participants. Conclusions and Relevance: In this nationally representative sample from 2005 to 2008, adolescent children identifying as Black, Mexican American, low-income, or non-US citizen were more likely to report poor subjective visual function and perform worse on objective visual acuity testing. A greater understanding of the underlying etiology of these disparities may yield opportunities for improving vision at the population level.
Oke I, Gaier E, Mantagos I, Shah A. Periodic trends in Internet Searches for Ocular Symptoms in the US. Ophthalmic Epidemiol. 2022;:1–6.
PURPOSE: To identify periodic trends in internet searches for ocular symptoms and to determine the seasonal peaks and troughs. METHODS: This cross-sectional study examined publicly available Google Trends data from the United States (01/01/2015 to 12/31/2019). A list of common ocular symptoms was compiled from the American Academy of Ophthalmology Eye Health website and Wills Eye Manual. Ocular symptoms were stratified into categories involving vision change, eye pain, or eye redness. The search volume over time for each term was modeled using periodic regression functions and the goodness-of-fit was reported. Fisher's exact tests were used to compare the characteristics of periodic vs. non-periodic query terms. RESULTS: Seasonal trends were demonstrated by 45% (48/106) of the ocular symptoms included in this investigation. Search terms with best fit to the periodic model included stye (r2 = 0.89), pink eye (r2 = 0.82), dry eye (r2 = 0.76), blurry vision (r2 = 0.72), and swollen eye (r2 = 0.71). Periodic search terms were more likely to involve eye redness (21% vs. 11%, p = .014) and less likely to involve vision change (11% vs. 36%; p < .001). Periodic queries involving eye redness most often peaked in the spring and those involving eye pain peaked in the summer. CONCLUSION: Ocular symptom queries directly reflect seasonal trends for allergic eye disease and ocular trauma. Search query analyses can serve as accurate epidemiological tools with research and real-world clinical applications.
Huh D, Wang J, Fliotsos M, Beal C, Boente C, Wisely E, De Andrade L, Lorch A, Ramanathan S, Reinoso M, Swamy R, Waxman E, Woreta F, Srikumaran D. Association Between Parental Leave and Ophthalmology Resident Physician Performance. JAMA Ophthalmol. 2022;140(11):1066–1075.
IMPORTANCE: Although parental leave is essential in enhancing resident wellness and fostering inclusive workplace environments, residents may often feel discouraged from using parental leave owing to perceived stigma and concerns about possible negative effects on their training. OBJECTIVE: To examine parental leave usage across multiple institutions and compare residency performance metrics between residents who took parental leave vs their peers who did not take leave. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional analysis conducted from April 1, 2020, to July 28, 2022, of educational records. Multicenter data were obtained from 10 Accreditation Council for Graduate Medical Education (ACGME)-accredited ophthalmology programs across the US. Included ophthalmology residents graduated between 2015 and 2019. Data were analyzed from August 15, 2021, to July 25, 2022. EXPOSURES: Performance metrics of residents who used parental leave during residency were compared with those of residents who did not take parental leave. MAIN OUTCOMES AND MEASURES: Measures of performance included the Ophthalmic Knowledge Assessment Program (OKAP) scores, ACGME milestones scores, board examination pass rates, research activity, and surgical volumes. RESULTS: Of the 283 ophthalmology residents (149 male [52.7%]) included in the study, 44 (15.5%) took a median (IQR) parental leave of 4.5 (2-6) weeks. There were no differences in average OKAP percentiles, research activity, average ACGME milestones scores, or surgical volume between residents who took parental leave and those who did not. Residents who pursued fellowship were less likely to have taken parental leave (odds ratio [OR], 0.43; 95% CI, 0.27-0.68; P < .001), and residents who practiced in private settings after residency were more likely to have taken parental leave (OR, 3.56; 95% CI, 1.79-7.08; P < .001). When stratified by sex, no differences were identified in performance between female residents who took parental leave compared with residents who did not take leave, except a mild surgical number difference in 1 subspecialty category of keratorefractive procedures (difference in median values, -2; 95% CI, -3.7 to -0.3; P = .03). CONCLUSIONS AND RELEVANCE: In this multicenter cross-sectional study, no differences in performance metrics were identified between residents taking parental leave compared with their peers. These findings may provide reassurance to trainees and program directors regarding the unlikelihood, on average, that taking adequate parental leave will affect performance metrics adversely.
Chapman J, Heidary G, Gise R. An overview of peripapillary hyperreflective ovoid mass-like structures. Curr Opin Ophthalmol. 2022;33(6):494–500.
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the ophthalmic findings associated with peripapillary hyperreflective ovoid mass-like structures (PHOMS) in both adult and pediatric patients. RECENT FINDINGS: PHOMS have recently been identified in a number of different ophthalmic disease entities ranging from nonpathologic to pathologic, including but not limited to anatomic abnormalities (tilting in myopia), optic nerve head drusen, optic disc edema from inflammation (optic neuritis, white dot syndromes), vascular insults (ischemic optic neuropathy, retinal vascular occlusion), and papilledema. The mechanism underlying the formation of PHOMS has not been fully elucidated although it has been hypothesized that PHOMS occur secondary to axoplasmic stasis from crowding at the optic nerve head. SUMMARY: Although the clinical significance of the presence of PHOMS remains unclear, PHOMS are associated with several disease processes. Understanding the mechanism behind their formation and their impact on optic nerve head structure and visual function may be relevant in patients with optic nerve head pathology. The presence of PHOMS may also correlate with disease severity and duration. Future studies to evaluate whether the formation of PHOMS may be useful as an early indicator of disease or a prognostic tool are warranted.
Vemula SK, Kim S, Muvavarirwa T, Bell J, Whitman M. Impaired Extraocular Muscle Innervation Is Present Before Eye Opening in a Mouse Model of Infantile Nystagmus Syndrome. Invest Ophthalmol Vis Sci. 2022;63(10):4.
Purpose: To determine if extraocular muscles (EOMs) from mice with nystagmus show abnormalities in myofiber composition and innervation, as seen in EOMs from human nystagmus patients, and to determine when in development those changes occur. Methods: Balb/c albino mice were crossed to pigmented mice to generate heterozygous mice, which were mated to create experimental litters containing albinos and wild-type controls. Orbits were harvested from adult animals (12 weeks old); on postnatal day (P)0, P10, P14, and P21; and from 6-week-old animals. EOM sections were collected from the intraorbital portion of the muscles. Sections were immunostained for slow and fast myosin and for neuromuscular junctions (NMJs). The proportion of each myofiber subtype and the density and size of NMJs were quantified. Initial innervation patterns were assessed using whole-mount immunostaining of embryonic day (E)13.5 embryos expressing IslMN:GFP. Results: Adult albino EOMs display an increased proportion of slow myofibers, larger slow myofibers, and a decreased density of NMJs-similar to human nystagmus patients. The percentage of NMJs on slow myofibers is also lower in albino animals. The initial innervation pattern of the incoming ocular motor neurons is normal in E13.5 albino embryos. Differences in the proportion of slow and fast myofiber subtypes are present as early as P14, and a lower percentage of NMJs on slow myofibers is present by P21. There is a lower density of NMJs on albino EOMs as early as P10, prior to eye opening. Conclusions: Changes in NMJ development observed before eye opening indicate that nystagmus is not solely secondary to poor vision.
Oke I, Hall N, Elze T, Miller J, Lorch A, Hunter D, IRIS Data Analytics Committees. Adjustable Suture Technique Is Associated with Fewer Strabismus Reoperations in the Intelligent Research in Sight Registry. Ophthalmology. 2022;129(9):1028–1033.
PURPOSE: To compare the reoperation rates after strabismus surgery with and without the adjustable suture technique. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or older in the Intelligent Research in Sight (IRIS®) Registry who underwent strabismus surgery between January 1, 2013, and December 31, 2018. METHODS: Data were collected from the electronic health records of practices participating in the IRIS Registry. The primary exposure of interest was use of the adjustable suture technique, identified by Current Procedural Terminology coding. MAIN OUTCOME MEASURES: The primary outcome was repeat strabismus surgery within 1 year of initial strabismus surgery. Odds ratios (ORs) were derived from a multivariable logistic regression model evaluating the association between the use of adjustable sutures and reoperation rate, adjusting for patient demographics and surgical factors. RESULTS: A total of 34 872 patients who underwent strabismus surgery during the study interval were identified: 72% underwent horizontal muscle surgery, 17% underwent vertical muscle surgery, and 11% underwent combined horizontal and vertical muscle surgery. Adjustable sutures were used in 18% of patients. The overall reoperation rate within 1 year of strabismus surgery was 7.7%. The 1-year reoperation rate was 6.0% for patients treated with adjustable sutures and 8.1% for patients treated without adjustable sutures (P < 0.001). The multivariable regression model revealed a statistically significant 30% decrease in the odds of reoperation within 1 year of surgery when adjustable sutures were used (OR, 0.70; 95% confidence interval [CI], 0.62-0.78), a 40% increase in those with a history of prior strabismus surgery (OR, 1.40; 95% CI, 1.28-1.53), and a 9% increase per decade of age at surgery (OR, 1.09; 95% CI, 1.06-1.11). CONCLUSIONS: In adults cared for in practices participating in the IRIS Registry, the adjustable suture technique was associated with a significantly lower reoperation rate within 1 year of undergoing horizontal or combined horizontal and vertical strabismus surgery. Adjustable suture use in vertical strabismus surgery alone did not reduce the 1-year reoperation rate significantly. A history of prior strabismus surgery was associated with increased odds of reoperation.
Ogawa Y, Dana R, Kim S, Jain S, Rosenblatt M, Perez V, Clayton J, Alves M, Rocha EM, Amparo F, Seo KY, Wang Y, Shen J, Oh JY, Vanathi M, Nair S, Na KS, Riemens A, Sippel K, Soifer M, Wang S, Trindade M, Kim MK, Yoon CH, Yagi R, Hiratsuka R, Ogawa M, Shimizu E, Sato Y, Pflugfelder S, Tsubota K. Multicenter prospective validation study for international chronic ocular graft-versus-host disease consensus diagnostic criteria. Ocul Surf. 2022;26:200–208.
PURPOSE: To validate the international chronic ocular graft-versus-host disease (GVHD) diagnostic criteria (ICCGVHD) compared to the National Institute of Health diagnostic criteria 2014 (NIH2014) for chronic ocular GVHD. METHODS: Between 2013 and 2019, the study enrolled 233 patients with or without chronic ocular GVHD combined with the presence or absence of systemic chronic GVHD in an internationally prospective multicenter and observational cohort from 9 institutions. All patients were evaluated for four clinical parameters of ICCGVHD. RESULTS: The relation between the ICCGVHD score (0-11) and NIH2014 eye score (0-4) was relatively high (r = 0.708, 95% CI: 0.637-0.767, p < 0.001). The sensitivity and specificity of ICCGVHD for NIH 2014 for 233 patients were 94.3% (95% CI: 89.6%-98.1%) and 71.7% (95% CI: 63.0-79.5%), respectively (cutoff value of the ICCGVHD score = 6). The positive predictive value was 77.1% (95% CI: 71.1%-82.1%), and the negative predictive value was 87.0% (95% CI:81.6-92.5%). For the patients with systemic GVHD (n = 171), the sensitivity and specificity were 94.2% and 67.2%, respectively (ICCGVHD-score cutoff value = 6). By receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.903 (95% CI: 0.859-0.948). For patients without systemic GVHD (n = 62), the sensitivity and specificity were 100% and 76.7%, respectively (ICCGVHD-score cutoff value = 6). The AUC was 0.891 (95% CI 0.673-1.000). CONCLUSIONS: Good sensitivity, specificity, predictive value and correlation were found between ICCGVHD and NIH2014. ICCGVHD scores ≥6 can be useful to diagnose ocular GVHD with or without systemic GVHD for clinical research.
Yang M, Fjærvoll H, Fjærvoll K, Wang N, Utheim T, Serhan C, Dartt DA. Sex-based differences in conjunctival goblet cell responses to pro-inflammatory and pro-resolving mediators. Sci Rep. 2022;12(1):16305.
Many conjunctival inflammatory diseases differ between the sexes and altered conjunctival goblet cells (CGCs) response is often involved. Inflammation is initiated by the release of pro-inflammatory mediators and terminated by the biosynthesis of specialized pro-resolution mediators (SPMs). Herein, we determined the sex-based difference in the responses of CGCs to inflammatory stimuli or pro-resolving lipid SPMs and their interaction with sex hormones. GCs were cultured from pieces of human conjunctiva in RPMI media. CGCs were transferred 24 h before the start of experiments to phenol red-free and FBS-free media to minimize exogenous hormones. RT-PCR, immunofluorescence microscopy (IF), and Western Blot (WB) were performed to determine the presence of sex hormone receptors. Cellular response to pro-inflammatory stimuli or SPMs was studied by measuring the increase in intracellular [Ca2+] ([Ca2+]i) using fura 2/AM microscopy. Use of RT-PCR demonstrated estrogen receptor (ER) α in 4/5 males and 3/3 females; ERβ in 2/4 males and 2/3 females; and androgen receptors (AR) in 3/3 male and 3/3 female CGCs. Positive immunoreactivity by IF and protein expression by WB was detected using antibodies for the ERα and ERβ in 3/3 males and 3/3 females, while AR were only present in males. Significantly different Ca2+ responses between sexes were found with carbachol only at 10-3 M, but not with histamine or leukotriene (LT) B4 at any concentration used. Incubation with dihydrotestosterone (DHT), estrone (E1), or estradiol (E2) at 10-7 M for 30 min significantly inhibited the LTB4-stimulated [Ca2+]i increase in male and female CGCs. Incubation with DHT, E1, and E2 overnight significantly inhibited the LTB4 response in females, while DHT and E2 significantly inhibited the LTB4 response in males. The SPM lipoxin A4 (LXA4) (10-9-10-8 M), but not the resolvins D1 or D2, induced an [Ca2+]i increase that was significantly higher in males compared to females. We conclude that male and female CGCs showed differences in the expression of sex hormone receptors. Treatment with sex hormones altered pro-inflammatory mediator LTB4-induced response. Males compared to females have a higher response to the ω-6-fatty acid derived SPM LXA4, indicating males may terminate inflammation in conjunctival goblet cells faster than females.