Publications

2020

Ashraf M, Shokrollahi S, Salongcay R, Aiello LP, Silva P. Diabetic retinopathy and ultrawide field imaging. Semin Ophthalmol. 2020;35(1):56–65.
The introduction of ultrawide field imaging has allowed the visualization of approximately 82% of the total retinal area compared to only 30% using 7-standard field Early Treatment Diabetic Retinopathy (ETDRS) photography. This substantially wider field of view, while useful in many retinal vascular diseases, is particularly important in diabetic retinopathy where eyes with predominantly peripheral lesions or PPL have been shown to have significantly greater progression rates compared to eyes without PPL. In telemedicine settings, ultrawide field imaging has substantially reduced image ungradable rates and increased rate of disease identification allowing care to be delivered more effectively. Furthermore, the use of ultrawide field fluorescein angiography allows the visualization of significantly more diabetic retinal lesions and allows more accurate quantification of total retinal nonperfusion, with potential implications in the management of diabetic retinopathy and diabetic macular edema. The focus of this paper is to review the current role of ultrawide field imaging in diabetic retinopathy and its possible future role in innovations for retinal image analysis such as artificial intelligence and vessel caliber measurements.
Lu SY, Rong SS, Wu Z, Huang C, Matsushita K, Ng TK, Leung C, Kawashima R, Usui S, Tam P, Tsujikawa M, Young A, Zhang M, Wiggs J, Nishida K, Tham C, Pang CP, Chen LJ. Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese. Clin Exp Ophthalmol. 2020;48(5):658–665.
BACKGROUND: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. METHODS: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis. RESULTS: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (P = .0019, OR = 4.55, I = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (P = .81, OR = 1.05; I = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects. CONCLUSIONS: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.
Seminario-Vidal L, Kroshinsky D, Malachowski S, Sun J, Markova A, Beachkofsky T, Kaffenberger B, Ergen E, Mauskar M, Bridges A, Calhoun C, Cardones A, Chen S, Chodosh J, Cotliar J, Davis M, DeNiro K, Dominguez A, Eljure-Téllez J, Femia A, Fox L, Guda A, Mitchell C, Mostaghimi A, Ortega-Loayza A, Owen C, Pasieka H, Rahnama-Moghadam S, Saeed H, Saunderson R, Shanbhag S, Sharon V, Strowd L, Venkatesh S, Wanat K, Wetter D, Worswick S, Micheletti R. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol. 2020;82(6):1553–1567.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.
Tomita Y, Cakir B, Liu CH, Fu Z, Huang S, Cho S, Britton W, Sun Y, Puder M, Hellström A, Talukdar S, Smith L. Free fatty acid receptor 4 activation protects against choroidal neovascularization in mice. Angiogenesis. 2020;23(3):385–394.
To examine whether free fatty acid receptor 4 (FFAR4) activation can protect against choroidal neovascularization (CNV), which is a common cause of blindness, and to elucidate the mechanism underlying the inhibition, we used the mouse model of laser-induced CNV to mimic angiogenic aspects of age-related macular degeneration (AMD). Laser-induced CNV was compared between groups treated with an FFAR4 agonist or vehicle, and between FFAR4 wild-type (Ffar4) and knock out (Ffar4) mice on a C57BL/6J/6N background. The ex vivo choroid-sprouting assay, including primary retinal pigment epithelium (RPE) and choroid, without retina was used to investigate whether FFAR4 affects choroidal angiogenesis. Western blotting for pNF-ĸB/NF-ĸB and qRT-PCR for Il-6, Il-1β, Tnf-α, Vegf, and Nf-ĸb were used to examine the influence of FFAR4 on inflammation, known to influence CNV. RPE isolated from Ffar4 and Ffar4 mice were used to assess RPE contribution to inflammation. The FFAR4 agonist suppressed laser-induced CNV in C57BL/6J mice, and CNV increased in Ffar4 compared to Ffar4 mice. We showed that the FFAR4 agonist acted through the FFAR4 receptor. The FFAR4 agonist suppressed mRNA expression of inflammation markers (Il-6, Il-1β) via the NF-ĸB pathway in the retina, choroid, RPE complex. The FFAR4 agonist suppressed neovascularization in the choroid-sprouting ex vivo assay and FFAR4 deficiency exacerbated sprouting. Inflammation markers were increased in primary RPE cells of Ffar4 mice compared with Ffar4 RPE. In this mouse model, the FFAR4 agonist suppressed CNV, suggesting FFAR4 to be a new molecular target to reduce pathological angiogenesis in CNV.
Gise R, Heidary G. Update on Pediatric Optic Neuritis. Curr Neurol Neurosci Rep. 2020;20(3):4.
PURPOSE OF REVIEW: The purpose of this review is to provide an update on advances in the understanding of pediatric demyelinating optic neuritis. RECENT FINDINGS: In the past decade, the disease phenotypes for demyelinating syndromes in children have been more clearly defined. Pediatric optic neuritis may present as a clinically isolated syndrome or in the setting of underlying neurologic disease. In addition to optic neuritis associated with multiple sclerosis or neuromyelitis optica, recent work has identified antibodies to the myelin oligodendrocyte glycoprotein (MOG IgG) as a unique demyelinating cause with distinct features regarding treatment and prognosis. The disease phenotypes for demyelinating pediatric optic neuritis have expanded. Treatment strategies vary and are not universally effective for each cause of demyelinating disease. Accurately distinguishing among these unique clinical syndromes is therefore critical for initiation of appropriate treatment to prevent disability, to maximize visual outcomes, and to provide insight into long-term prognosis.
Hanyuda A, Rosner B, Wiggs J, Willett W, Tsubota K, Pasquale L, Kang J. Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: data from three US cohorts. Eye (Lond). 2020;34(8):1465–1475.
BACKGROUND/OBJECTIVES: To assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis. SUBJECTS/METHODS: We followed 185,638 participants of three large US prospective cohorts biennially (1976-2016, 1986-2016 and 1991-2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). RESULTS: There was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95% CI, 0.91-1.39; P = 0.40) for the overall score; 1.10 (95% CI, 0.89-1.35; P = 0.38) for the animal score and 0.96 (95% CI, 0.79-1.18; P = 0.88) for the vegetable score. No differential associations by IOP level was found (P ≥ 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95% CI, 0.55-1.10]; P = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95% CI, 0.83-1.44]; P = 0.14; P = 0.03). CONCLUSIONS: Low-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss.
Busch C, Okada M, Zur D, Fraser-Bell S, Rodríguez-Valdés P, Cebeci Z, Lupidi M, Fung A, Gabrielle PH, Giancipoli E, Chaikitmongkol V, Laíns I, Santos AR, Kunavisarut P, Sala-Puigdollers A, Chhablani J, Ozimek M, Hilely A, Degenhardt V, Loewenstein A, Iglicki M, Rehak M, International Retina Group. Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity. Acta Ophthalmol. 2020;98(7):e801-e806.
PURPOSE: To investigate clinical baseline characteristics and optical coherence tomography biomarkers predicting visual loss during observation in eyes with diabetic macular oedema (DMO) and good baseline visual acuity (VA). METHODS: A sub-analysis of a 12-month, retrospective study, including patients with baseline VA ≤0.1 logMAR (≥20/25 Snellen) and centre-involving DMO. The primary outcome measure was the correlation between baseline characteristics and VA loss ≥10 letters during follow-up. RESULTS: A total of 249 eyes were included in the initial study, of which 147 eyes were observed and 80 eyes received anti-vascular endothelial growth factor (VEGF) treatment at baseline. Visual acuity (VA) loss ≥10 letters occurred in 21.8% (observed cohort) and in 24.3% (treated cohort), respectively. Within observed eyes, presence of hyperreflective foci [HRF; odds ratio (OR): 3.18, p = 0.046], and disorganization of inner retina layers (DRIL; OR: 2.71, p = 0.026) were associated with a higher risk of VA loss ≥10 letters. In observed eyes with a combined presence of HRF, DRIL and ellipsoid zone (EZ) disruption, the risk of VA loss was further increased (OR: 3.86, p = 0.034). In eyes with combined presence of DRIL, HRF and EZ disruption, risk of VA loss was 46.7% (7/15 eyes) in the observed cohort, and 26.3% (5/19 eyes) in the treated cohort (p = 0.26). CONCLUSION: Patients with DMO and good baseline VA, managed by observation, are of increased risk for VA loss if DRIL, HRF and EZ disruption are present at baseline. Earlier treatment with anti-VEGF in these patients may potentially decrease the risk of VA loss at 12 months.
Parikh R, Palmer V, Kumar A, Simon J. Surgical Confusions in Ophthalmology: Description, Analysis, and Prevention of Errors from 2006 through 2017. Ophthalmology. 2020;127(3):296–302.
PURPOSE: To characterize surgical confusions in ophthalmology to determine their incidence, root causes, and impact on patients and physicians. DESIGN: Retrospective cohort study of errors in ophthalmic surgical procedures between January 1, 2006, and December 31, 2017. PARTICIPANTS: One hundred forty-three cases involving surgical confusions. METHODS: Cases were identified by the Ophthalmic Mutual Insurance Company from closed case files and by the New York State Health Department from the New York Patient Occurrence Reporting and Tracking program that identified the surgical confusions. MAIN OUTCOME MEASURES: Incidence and impact by intended surgery, error type, and root cause as well as preventability by the Universal Protocol. RESULTS: Of the 143 cases of surgical confusions identified, 92 cases (64.3%) were deemed preventable by the Universal Protocol. Approximately two thirds, 95 cases (66.4%), were cases of incorrect implants being used during cataract surgery (cataract extraction and intraocular lens implantation), of which 33 cases (34.7%) were not preventable by the Universal Protocol. Wrong eye blocks or anesthesia accounted for 20 cases (14.0%), incorrect eye procedures accounted for 10 cases (7.00%), incorrect refractive surgery measurements accounted for 6 cases (4.20%), incorrect patient or procedure accounted for 5 cases (3.50%), incorrect intraocular gas concentration accounted for 4 cases (2.80%), and incorrect medication in surgery accounted for 3 cases (2.10%). The most common root cause of confusion was an inadequately performed time out, which was responsible for nearly one third of all surgical confusions, 46 cases (32.2%). Incorrect lens orders or calculations before surgery (so-called upstream errors) were the second most common cause of surgical confusion, involving 31 cases (21.7%). The average legal indemnity for incorrect implant during cataract surgery was $57 514 (United States dollars). The average indemnity for incorrect refractive surgery measurement was $123 125, that for incorrect eye procedure was $50 000, and that for incorrect gas concentration was $220 844. CONCLUSIONS: Most surgical confusions could have been prevented by following the Universal Protocol properly. However, upstream errors, originating in the clinic or office before surgery, and ineffective communication during time outs suggest a need for modification of the Universal Protocol.