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Adomfeh J, Chinn RN, Michalak SM, Shoshany TN, Bishop K, Hunter DG, Jastrzembski BG, Oke I. Association of Neighborhood Child Opportunity Index with presenting visual acuity in amblyopic children. J AAPOS 2023;27(1):20.e1-20.e5.Abstract
PURPOSE: To demonstrate the use of a novel measure of neighborhood quality, the Child Opportunity Index (COI), for investigating health disparities in pediatric ophthalmology. METHODS: This study included children 2-12 years of age from a registry of patients diagnosed with amblyopia at an urban pediatric hospital between 2010 and 2014. Children previously treated for amblyopia were excluded. Patient demographics, residential addresses, and logMAR visual acuities were collected. The association between visual acuity at presentation and COI was examined using linear mixed-effects models adjusting for individual-level factors, including age, sex, race, ethnicity, and insurance type. RESULTS: This study included 1,050 amblyopic children, of whom 317 (37%) were non-White and 149 (19%) were Hispanic; 461 (44%) had public insurance. Regarding residence, 129 (12%) lived in areas of very low opportunity (COI <20); 489 (47%) in areas of very high opportunity (COI ≥80). Children residing in the lowest opportunity neighborhoods correctly identified approximately two fewer letters at presentation with their better-seeing eye compared with children from the highest opportunity neighborhoods after adjusting for individual-level factors (-0.0090 logMAR per 20 unit increase in COI; 95% CI, -0.0172 to -0.0008; P = 0.031). No difference was appreciated in the worse-seeing eye. CONCLUSIONS: Amblyopic children residing in communities with low neighborhood opportunity had slightly worse visual acuity in the better-seeing eye at presentation. Although statistically significant in the better-seeing eye, the two-letter difference attributable to neighborhood environment may not be clinically significant, and the impact of this disparity on treatment outcomes deserves further investigation.
Zoumpou T, Samuel S, Torun N, Yadav P, Jones DB. Floppy Eyelid Syndrome: an Overlooked Comorbidity Among Bariatric Patients. Obes Surg 2023;33(2):523-529.Abstract
PURPOSE: Floppy eyelid syndrome (FES) is a clinical entity characterized by palpebral hyperlaxity and chronic conjunctivitis. Patients' eyelids evert ("flip inside out"), leading to eye irritation, dryness, grittiness, and tearing. More severe cases can lead to significant ocular complications, such as keratoconus and impaired eyesight. Research has revealed an association between FES and obstructive sleep apnea syndrome (OSAS). OSAS is also one of the most common comorbidities among patients with obesity and an indication for bariatric surgery. This is one of the first studies to explore FES in a group of patients who have undergone bariatric surgery. MATERIALS AND METHODS: This was a retrospective study. A total of 88 patients completed a survey by mail or telephone. Additional data on demographics and baseline preoperative clinical information was extracted from the online medical records and the MBSAQIP database. RESULTS: Thirty-nine patients (44%) recalled having chronic ocular symptoms before their bariatric surgery, among whom six reported palpebral laxity and/or an established diagnosis of FES. The majority of them (67%) rated their symptoms postoperatively as "somewhat" or "significantly improved." The patients that reported improvement in their ocular symptoms also experienced an improvement in their OSAS severity. CONCLUSION: Bariatric surgery might affect the clinical course of FES and the severity of symptoms. Treating OSAS, the underlying mechanism of FES, is a possible mechanism of how bariatric surgery can help patients. It is also critical for bariatric surgeons to consider FES when patients with obesity, particularly those with OSAS, present with chronic eye symptoms.
Nakao T, Inomata T, Blanco T, Musayeva A, Tahvildari M, Amouzegar A, Yin J, Chauhan SK, Chen Y, Dana R. Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice. Transplantation 2023;107(6):1302-1310.Abstract
BACKGROUND: Corneal transplantation outcomes are generally less favorable in young children compared with adults. The purpose of this study was to determine the immunological mechanisms underlying this difference. METHODS: A murine model of allogeneic corneal transplantation was used in the study, and graft survival was determined by evaluating opacity scores for 8 wk. Syngeneic transplantation in the very young host served as a surgical control. The frequencies of total and activated natural killer (NK) cells in cornea posttransplantation were kinetically evaluated using flow cytometry. The regulatory T cell (Treg) frequency and function in naive animals were assessed by flow cytometry and in vitro suppression assays, respectively. Finally, graft survival and immune responses were determined in NK cell-depleted, or adult naive Treg-transferred, young hosts. RESULTS: Corneal allograft survival in the very young recipients was significantly lower than in adult hosts. The frequencies of total NK cells and their interferon gamma-expressing subset in the cornea were significantly higher in the very young mice posttransplantation. In ungrafted mice, frequencies of Treg in draining lymph nodes as well as their capabilities to suppress NK-cell secretion of interferon gamma were lower in the very young compared with adults. In NK cell-depleted or adult Treg--transferred very young recipients, the allograft survival was significantly improved along with the suppressed NK-cell response. CONCLUSIONS: Our data demonstrate that amplified activity of NK cells, together with lower suppressive function of Treg, contributes to early rejection of corneal allografts in very young graft recipients.
Wu AM, Shen LQ. Racial Disparities Affecting Black Patients In Glaucoma Diagnosis And Management. Semin Ophthalmol 2023;38(1):65-75.Abstract
Black patients are more affected by glaucoma and suffer from more advanced disease. Diagnostic challenges among black patients with glaucoma include lower rates of diagnostic testing and thinner average central corneal thickness, the latter of which affects intraocular pressure measurement. Treatment challenges include poor follow-up, medication adherence, and trust in providers. Black patients undergoing trabeculectomy have higher rates of failure compared to white patients. Race is not a definitive factor affecting success for tube shunts, laser trabeculoplasty, cyclophotocoagulation, and micro-invasive glaucoma surgeries, but the body of evidence is limited by low inclusion of black patients in these studies. Future steps should include increased attention toward improving trust between patients and providers, improving access to care, and increased representation of black patients in glaucoma research to better understand factors affecting racial disparities in glaucoma management and outcomes in this population disproportionately affected by the disease.
Vignal-Clermont C, Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Subramanian PS, Wang A-G, Donahue SP, Leroy BP, Sadun AA, Klopstock T, Sergott RC, Rebolleda Fernandez G, Chwalisz BK, Banik R, Taiel M, Roux M, Sahel J-A, Sahel J-A. Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy. Am J Ophthalmol 2023;249:108-125.Abstract
PURPOSE: To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy. DESIGN: Pooled analysis of safety data from 5 clinical studies. METHODS: A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2. RESULTS: Almost all patients (95.2%) received 9 × 1010 viral genomes and 87.8% had at least 2 years of follow-up. Most patients (75.1%) experienced at least one systemic AE, but systemic treatment-related AEs occurred in 3 patients; none were serious. Intraocular inflammation was reported in 75.6% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflammations occurred in the anterior chamber (58.8%) or in the vitreous (40.3%), and were of mild (90.3%) or moderate (8.8%) intensity; most resolved with topical corticosteroids alone. All IOP increases were mild to moderate in intensity. No AE led to study discontinuation. Bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was comparable for patients treated bilaterally and unilaterally. CONCLUSIONS: Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.
Yavuz Saricay L, Baldwin G, Leake K, Johnston A, Shah AS, Patel NA, Gonzalez E. Cytomegalovirus retinitis and immune recovery uveitis in a pediatric patient with leukemia. J AAPOS 2023;27(1):52-55.Abstract
Immune recovery uveitis (IRU) is an ocular form of immune reconstitution inflammatory syndrome, which is rare in the pediatric population. We report a case of IRU in an 11-year-old girl with a history of cytomegalovirus (CMV) retinitis in the setting of acute leukemia, who developed uveitis, vitritis, retinitis, and vasculitis during immune reconstitution. She was found to have negative CMV antigenemia, and the disease occurred during concurrent systemic antiviral therapy. Anterior chamber tap confirmed the absence of the CMV in the eye, and recurrent blood samples continued to reveal absent CMV viral particles systemically while her lymphocyte count was steadily increasing. The patient responded to oral steroids, leading to resolution of active retinitis. Tapering the steroids caused a mild reactivation of the ocular immune response.
De Arrigunaga S, Akpek EK, Aldave AJ, Mian SI, Zurakowski D, Ciolino JB, Ciolino JB. Prospective, Randomized, Multicenter, Double-Masked, Clinical Trial of Corneal Cross-Linking for Boston Keratoprosthesis Carrier Tissue. Am J Ophthalmol 2023;249:39-48.Abstract
PURPOSE: To assess whether cross-linking the carrier donor cornea of the Boston Keratoprosthesis (BKPro) improves retention of the device in participants at high risk for keratolysis. DESIGN: Prospective, double-masked, randomized clinical trial. METHODS: In this multicenter study, 68 adult participants who were scheduled for BKPro implantation were enrolled. Masked participants were randomized to receive either a cross-linked (CXL) or non-cross-linked (non-CXL) donor corneal carrier. The Kaplan-Meier event-free survival was determined by the product-limit method and compared by the log-rank test to examine whether survival curves were different between the CXL and non-CXL groups. The primary outcome of the study was time from surgery to BKPro removal. The secondary endpoint was 12-month retention rate. RESULTS: A total of 68 participants were enrolled and randomized 1:1 to each group. The average age at the time of surgery was 62 (range = 24-89) years, and 42 participants (62%) were male. The overall BKPro retention rate was 70% during a mean follow-up time of 93 (range = 6-201) weeks. Twenty BKPros were removed, 10 in the CXL group and 10 in the non-CXL group, with 18 requiring removal because of sterile keratolysis. There was no difference in the time to removal between the groups during the study (P = .910). At 12 months, there was no significant difference in the retention rate in the CXL group (94%) vs the non-CXL group (82%, P = .150). CONCLUSIONS: In this prospective study, cross-linking of the carrier cornea prior to BKPro implantation did not reduce the incidence of sterile keratolysis or increase device retention among participants at high risk for retention failure.
Sit AJ, Chen TC, Takusagawa HL, Rosdahl JA, Hoguet A, Chopra V, Richter GM, Ou Y, Kim SJ, WuDunn D. Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk: A Report by the American Academy of Ophthalmology. Ophthalmology 2023;130(4):433-442.Abstract
PURPOSE: To review the current published literature on the utility of corneal hysteresis (CH) to assist the clinician in the diagnosis of glaucoma or in the assessment of risk for disease progression in existing glaucoma patients. METHODS: Searches of the peer-reviewed literature in the PubMed database were performed through July 2022. The abstracts of 423 identified articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 19 articles were selected, and the panel methodologist rated them for level of evidence. Eight articles were rated level I, and 5 articles were rated level II. The 6 articles rated level III were excluded. RESULTS: Corneal hysteresis is lower in patients with primary open-angle glaucoma, primary angle-closure glaucoma, pseudoexfoliative glaucoma, and pseudoexfoliation syndrome compared with normal subjects. Interpretation of low CH in patients with high intraocular pressure (IOP) or on topical hypotensive medications is complicated by the influence of these parameters on CH measurements. However, CH is also lower in treatment-naïve, normal-tension glaucoma patients compared with normal subjects who have a similar IOP. In addition, lower CH is associated with an increased risk of progression of glaucoma based on visual fields or structural markers in open-angle glaucoma patients, including those with apparently well-controlled IOP. CONCLUSIONS: Corneal hysteresis is lower in glaucoma patients compared with normal subjects, and lower CH is associated with an increased risk of disease progression. However, a causal relationship remains to be demonstrated. Nevertheless, measurement of CH complements current structural and functional assessments in determining disease risk in glaucoma suspects and patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Phanphruk W, Hennein L, Hunter DG. Strabismus Surgery in Orthophoric Patients With Symptomatic, Asymmetric Vertical or Horizontal Incomitance. Am J Ophthalmol 2023;249:29-38.Abstract
PURPOSE: To report the indications, operative strategies, and surgical outcomes of patients who undergo vertical and horizontal rectus muscle surgery for incomitant strabismus despite being orthophoric in primary gaze. DESIGN: Retrospective, interventional case series. METHODS: The setting for this study was an academic practice at Boston Children's Hospital. The patient population comprised 8 orthophoric patients who underwent strabismus surgery to treat vertical/horizontal incomitance. Observation procedures included review of surgical strategies, strabismus measurements in diagnostic gaze positions, and development of postoperative diplopia. The main outcome measures were preserved single vision in primary gaze, comitance, reoperation rate, and patient/surgeon satisfaction. RESULTS: Surgical strategies included the following: (1) simultaneous recession of ipsilateral antagonist rectus muscles; (2) recession or resection of 1 rectus muscle with balancing surgery on the fellow eye; (3) restricting the range of 1 muscle (combined resection and recession or posterior fixation suture); and (4) creating an acceptable deviation in primary gaze. Mean follow-up was 5.4 months (median, 2 months; range, 2-25 months). No patient had new-onset primary gaze diplopia. The median incomitance improved by 9.5 prism diopters. No patient required additional surgery. Patient satisfaction and surgeon assessment of outcomes were high. CONCLUSIONS: Although the risk of operating on orthophoric patients with incomitant strabismus may discourage surgeons from offering treatment, the use of specific strategies to address incomitance can preserve alignment in primary gaze while improving patient satisfaction. These strategies may also benefit patients with incomitant strabismus that is symptomatic in primary gaze.
Gluckstein J. Diversity in Academic Ophthalmology: Disparities and Opportunities from Medical School to Practice. Semin Ophthalmol 2023;38(4):338-343.Abstract
INTRODUCTION: Compared to the United States population as a whole, physicians are more likely to identify as men, identify as Asian or non-hispanic White, and be raised in wealthier households. Racial, ethnic, gender, and socioeconomic representation in ophthalmology is often blamed on the pipeline of matriculants. METHODS: This review collects recent data from the US census, AAMC, and primary literature on gender, racial, ethnic, and socioeconomic diversity from medical school to ophthalmology practice. RESULTS: Data from the medical and ophthalmology literature shows that medical students are less diverse than medical school applicants, ophthalmology residencies are less diverse than graduating medical students, and ophthalmology departments are less diverse than those of most other specialties. DISCUSSION: At each level, there are limitations in representation beyond the pipeline of medical school applicants or medical students applying to ophthalmology. There are many practical steps the field can take at each level of training to move the specialty toward more equitable representation.
Baker CW, Josic K, Maguire MG, Jampol LM, Martin DF, Rofagha S, Sun JK, Sun JK. Comparison of Snellen Visual Acuity Measurements in Retinal Clinical Practice to Electronic ETDRS Protocol Visual Acuity Assessment. Ophthalmology 2023;130(5):533-541.Abstract
PURPOSE: Evaluate the differences between clinical visual acuity (VA) as recorded in medical records and electronic Early Treatment Diabetic Retinopathy Study (eETDRS) protocol VA measurements and factors affecting the size of the differences. DESIGN: Retrospective chart review. PARTICIPANTS: Study and fellow eyes of participants enrolled in DRCR Retina Network Protocols AC and AE (diabetic macular edema), and W (nonproliferative diabetic retinopathy) with clinical VA recorded within 3 months before the protocol visit. METHODS: Differences and their association with patient and ocular factors were evaluated using linear mixed models with random effects for correlations within sites and participants. MAIN OUTCOME MEASURE: Difference between VA letter scores measured by eETDRS during a study visit versus measured by Snellen during a regular clinical visit (Snellen fraction converted to eETDRS). RESULTS: Data from 1016 eyes (511 participants) across 74 sites were analyzed. The mean VA measurements were 68.6 letters (Snellen equivalent 20/50) at the clinical visit and 76.3 letters (Snellen equivalent 20/32) at the protocol visit, with a mean (standard deviation [SD]) of 26 (21) days between visits. Mean (SD) protocol VA was better than clinical VA by 7.6 (9.6) letters overall, 10.7 (12.6) letters in eyes with clinical VA ≤ 20/50 (n = 376), and 5.8 (6.6) letters in eyes with clinical VA ≥ 20/40 (n = 640). On average, the difference between clinical and protocol VA was 1.3 letters smaller for every 1-line (5 letters) increase in clinical VA (P < 0.001). Mean (SD) differences by clinical correction of refractive error were 3.9 (9.0) letters with refraction, 6.9 (9.2) letters with glasses/contact lenses, 7.9 (11.5) letters with pinhole, and 9.8 (9.3) letters without correction (P = 0.06). CONCLUSIONS: On average, clinical Snellen VA is 1 to 2 lines worse than eETDRS protocol refraction and VA testing, which may partly explain why clinical practice does not always replicate clinical trial results. Eyes with lower clinical measurements and eyes tested without clinical refraction tended to have larger differences. Considering the potential discrepancies between clinical and protocol VA measurements, refracting eyes in the clinic may benefit patients when determining treatment plans and study referrals based on vision. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Hennein L, Jastrzembski B, Shah AS. Use of Telemedicine in Pediatric Ophthalmology in the Underserved Population. Semin Ophthalmol 2023;38(2):116-123.Abstract
Access to pediatric eye care is critical in diagnosing and treating eye disease promptly to prevent visual impairment. The demand for pediatric ophthalmology is high, even in developed countries, and significant socioeconomic disparities exist in access to care. The purpose of this article is to summarize the current literature on the use of telemedicine in pediatric ophthalmology in the underserved population and to identify areas of opportunity. A detailed literature review was performed in PubMed and Google Scholar on October 1, 2021. All articles in English that described the use of telemedicine in pediatric ophthalmology, with particular attention to the underserved pediatric population, were included. There is a paucity of literature on the visual outcomes from pediatric teleophthalmology alone, and even less in underserved populations specifically. Literature supports its use in subacute to chronic eye disease, return and postoperative visits, and screening for retinopathy in prematurity in particular. Collaboration between pediatric optometrists and pediatric ophthalmologists for both asynchronous and synchronous care delivery models has shown promise in several studies. It is essential to operate within the limits of pediatric teleophthalmology and utilize this valuable service for its strengths. Telemedicine may expand access to pediatric ophthalmologists in underserved populations and may reduce the burden of eye disease.

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