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North VS, Habib L, Yoon MK. Merkel Cell Carcinoma of the Eyelid: a Review. Surv Ophthalmol 2019;Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive tumor of both epithelial and neuroendocrine origin that carries a mortality rate of up to 40%. MCC tumors typically present as painless, expanding nodules on the sun-exposed skin areas of older, white patients. Eyelid and periocular tumors comprise approximately 2.5% of all cases of MCC and may be mistaken for chalazia or basal cell carcinomas. Immunosuppression is a significant risk factor, particularly in solid-organ transplant recipients, patients with chronic lymphocytic leukemia, and patients with HIV. Sentinel lymph node biopsy is often employed for accurate staging of head and neck MCC. Treatment includes wide-local excision, commonly with the addition of radiotherapy for improved locoregional disease control. Historically, adjuvant chemotherapy had been reserved for metastatic disease, but immunotherapy and targeted chemotherapies are currently being investigated for use in primary disease. The clinical characteristics of all available published cases of eyelid MCC are summarized .
Ichhpujani P, Singh RB, Foulsham W, Thakur S, Lamba AS. Visual implications of digital device usage in school children: a cross-sectional study. BMC Ophthalmol 2019;19(1):76.Abstract
PURPOSE: To evaluate the use of digital devices, reading habits and the prevalence of eyestrain among urban Indian school children, aged 11-17 years. METHODS: The study included 576 adolescents attending urban schools who were surveyed regarding their electronic device usage. Additional information on the factors that may have an effect on ocular symptoms was collected. RESULTS: Twenty percent of students aged 11 in the study population use digital devices on a daily basis, in comparison with 50% of students aged 17. In addition to using these devices as homework aids, one third of study participants reported using digital devices for reading instead of conventional textbooks. The majority of students preferred sitting on a chair while reading (77%; 445 students), with only 21% (123 students) preferring to lie on the bed and 8 students alternating between chair and bed. There was a significant association between the students who preferred to lie down and those who experienced eyestrain, as reported by a little over one fourth of the student population (27%). Out of 576 students, 18% (103) experienced eyestrain at the end of the day after working on digital devices. CONCLUSIONS: The increased use of digital devices by adolescents brings a new challenge of digital eyestrain at an early age. Our study reports the patterns of electronic device usage by school children, evaluates factors associated with eyestrain and highlights the need for further investigation of these issues.
Chung DC, Bertelsen M, Lorenz B, Pennesi ME, Leroy BP, Hamel CP, Pierce E, Sallum J, Larsen M, Stieger K, Preising M, Weleber R, Yang P, Place E, Liu E, Schaefer G, DiStefano-Pappas J, Elci OU, McCague S, Wellman JA, High KA, Reape KZ. The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene. Am J Ophthalmol 2019;199:58-70.Abstract
PURPOSE: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. DESIGN: Global, multicenter, retrospective chart review. METHODS: Study Population: Seventy individuals with biallelic RPE65 mutation-associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). RESULTS: VA decreased with age in a nonlinear, positive-acceleration relationship (P < .001). GVF decreased with age (P < .0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P = .0114, left eye; P = .0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. CONCLUSIONS: The number of clinical diagnoses and lack of a consistent RPE65 mutation-to-phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.
Al-Moujahed A, Tian B, Efstathiou NE, Konstantinou EK, Hoang M, Lin H, Miller JW, Vavvas DG. Receptor interacting protein kinase 3 (RIP3) regulates iPSCs generation through modulating cell cycle progression genes. Stem Cell Res 2019;35:101387.Abstract
The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82%). RNA-seq analysis and qRT-PCR showed that RIP3 KO MEFs expressed lower levels of genes that control cell cycle progression and cell division and higher levels of extracellular matrix-regulating genes. The growth rate of RIP3 KO MEFs was significantly slower than WT MEFs. These findings can partially explain the inhibitory effects of RIP3 deletion on iPSCs generation and show for the first time that the necroptosis kinase RIP3 plays an important role in iPSC reprogramming. In contrast to RIP3, the kinase and scaffolding functions of RIPK1 appeared to have distinct effects on reprogramming.
Tieger MG, Jakobiec FA, Ma L, Wolkow N. Small Benign Storiform Fibrous Tumor (Fibrous Histiocytoma) of the Conjunctival Substantia Propria in a Child: Review and Clarification of Biologic Behavior. Ophthalmic Plast Reconstr Surg 2019;35(5):495-502.Abstract
PURPOSE: A case of a small benign storiform fibrous tumor of the conjunctival substantia propria is described to clarify the category of fibrous histiocytoma. In addition, a comparison of the various spindle cell tumors of the conjunctival substantia propria is explored. METHODS: The patient underwent a complete tumor excision, and the specimen was analyzed by histopathologic and immunohistochemical investigations. RESULTS: A cellular mass, composed solely of spindle cells in a storiform pattern without a component of histiocytic cells, was found beneath an undisturbed nonkeratinizing squamous epithelium and was separated from the epithelium by a grenz zone of uninvolved collagen. The lesion was sharply demarcated but not encapsulated. The Masson trichrome stain revealed scant deposition of intercellular collagen. The reticulin stain displayed numerous and delicate wiry fibers between the tumor cells and encircling capillaries. The Alcian blue stain demonstrated faint positivity in the interstitium. Immunohistochemistry revealed positivity for vimentin, factor XIIIa, smooth muscle actin, CD10, and CD45. Negative stains were obtained for CD34, CD56, S100, desmin, and Ki67. CONCLUSIONS: The broad term of fibrous histiocytoma should be reserved for deep fibroblastic spindle cell tumors (e.g., those of the orbit) that display an aggressive behavior. More benign superficial spindle cell tumors of the dermis are now preferentially characterized as dermatofibromas. It is suggested that equally benign epibulbar tumors should no longer be designated as fibrous histiocytomas but rather as benign storiform fibrous tumors. Tumors completely composed of polygonal histiocytoid (epithelioid) cells that are CD34+ should be excluded from the benign storiform fibrous tumor category. Positive smooth muscle actin and factor XIIIa staining in conjunction with negative staining for CD34 and desmin in the current spindled tumor cells are findings consistent with those of cutaneous dermatofibromas. Both the epibulbar and dermal spindle cell lesions have displayed an indolent and nonaggressive behavior. Microscopically they contain a high proportion of dendrocytic stellate cells that are either factor XIIIa+ or XIIIa-. Given the anatomic differences between the dermis and conjunctiva, the term dermatofibroma is inappropriate for the current tumor; instead the term benign storiform fibrous tumor has been proposed for superficial tumors of the conjunctiva.
Rong SS, Lu SY, Matsushita K, Huang C, Leung CKS, Kawashima R, Usui S, Tam POS, Young AL, Tsujikawa M, Zhang M, Nishida K, Wiggs JL, Tham CC, Pang CP, Chen LJ. Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese. Exp Eye Res 2019;180:129-136.Abstract
The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (P = 4.3 × 10, OR = 0.72, I = 0). Additionally, we replicated the association of one known SNP, rs33912345 (P = 0.0061, OR = 0.69, I = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (P = 0.017, OR = 0.70, I = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (P<0.005). Furthermore, two haplotypes, C-C (P = 1.13 × 10, OR = 1.41, I = 0) and A-A (P = 0.045, OR = 0.68, I = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG.
Lin MM, Rageh A, Turalba AV, Lee H, Falkenstein IA, Hoguet AS, Ojha P, Rao VS, Ratanawongphaibul K, Rhee DJ, Shen LQ, Song BJ, Chen TC. Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma. J Glaucoma 2019;28(5):473-480.Abstract
PRéCIS:: This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure (IOP) to a greater degree in angle-closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma. PURPOSE: Endocyclophotocoagulation (ECP) laser treatment of the ciliary processes is believed to decrease IOP by reducing aqueous production. Anecdotal experience in angle-closure glaucoma suggests that it may also lower IOP by opening the drainage angle to promote aqueous outflow. This study sought to evaluate combined phacoemulsification and ECP (phaco/ECP) in eyes with different types and stages of glaucoma. PATIENTS AND METHODS: A Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution was conducted. RESULTS: In 63 eyes of 63 patients with an average of 3.0±1.7 years of follow-up, the 22 eyes with chronic angle-closure glaucoma (CACG) had greater IOP reduction and medication reduction than the 41 eyes with primary open-angle glaucoma at both 1 year (6.4 vs. 2.1 mm Hg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4 mm Hg, P=0.02; 0.9 vs. 0.3 medications, P=0.05). There was no difference in IOP reduction or medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11; 0.1, 0.8, 0.4 medications, P=0.14). CONCLUSIONS: Eyes with CACG were more responsive to phaco/ECP in terms of IOP and medication reduction compared with eyes with primary open-angle glaucoma. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Phaco/ECP was effective in all stages of glaucoma.
Farinha CVL, Cachulo ML, Alves D, Pires I, Marques JP, Barreto P, Nunes S, Costa J, Martins A, Sobral I, Laíns I, Figueira J, Ribeiro L, Cunha-Vaz J, Silva R. Incidence of Age-Related Macular Degeneration in the Central Region of Portugal: The Coimbra Eye Study - Report 5. Ophthalmic Res 2019;:1-10.Abstract
PURPOSE: To describe the 6.5-year incidence and progression of age-related macular degeneration (AMD) in a coastal town of central Portugal. METHODS: Population-based cohort study. Participants underwent standardized interviews and ophthalmological examination. Color fundus photographs were graded according to the International Classification and Grading System for AMD and ARM. The crude and age-standardized incidence of early and late AMD was calculated, and progression was analyzed. RESULTS: The 6.5-year cumulative incidence of early AMD was 10.7%, and of late AMD it was 0.8%. The incidence of early AMD was 7.2, 13.1 and 17.7% for participants aged 55-64, 65-74 and 75-84 years (p < 0.001). The late AMD incidence was 0.3, 0.9 and 2.8% for the corresponding age groups (p = 0.003). The age-standardized incidence was 10.8% (95% CI, 10.74-10.80%) for early and 1.0% (95% CI, 1.00-1.02%) for late AMD. The incidence of both neovascular AMD and geographic atrophy was 0.4%. Progression occurred in 17.2% of patients. CONCLUSION: The early AMD incidence in a coastal town of central Portugal was found to be similar to that of major epidemiological studies of European-descent populations; however, the incidence of late AMD was lower, and further analysis on risk factors will be conducted.
Burstein R, Noseda R, Fulton AB. Neurobiology of Photophobia. J Neuroophthalmol 2019;39(1):94-102.Abstract
BACKGROUND: Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is processed have paved the way to a better understanding of the neurobiology of photophobia and the complexity of the symptoms triggered by light. PURPOSE: The purpose of this review is to summarize recent anatomical and physiological studies on the neurobiology of photophobia with emphasis on migraine. RECENT FINDINGS: Observations made in blind and seeing migraine patients, and in a variety of animal models, have led to the discovery of a novel retino-thalamo-cortical pathway that carries photic signal from melanopsinergic and nonmelanopsinergic retinal ganglion cells (RGCs) to thalamic neurons. Activity of these neurons is driven by migraine and their axonal projections convey signals about headache and light to multiple cortical areas involved in the generation of common migraine symptoms. Novel projections of RGCs into previously unidentified hypothalamic neurons that regulate parasympathetic and sympathetic functions have also been discovered. Finally, recent work has led to a novel understanding of color preference in migraine-type photophobia and of the roles played by the retina, thalamus, and cortex. SUMMARY: The findings provide a neural substrate for understanding the complexity of aversion to light in patients with migraine and neuro-ophthalmologic other disorders.
Wolkow N, Jakobiec FA, Habib LA, Freitag SK. Orbital Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma: An Ongoing Diagnostic Challenge Further Confounded by Small-Cell Predominance. Ophthalmic Plast Reconstr Surg 2019;35(5):478-483.Abstract
PURPOSE: To highlight the histopathologic diagnostic challenges of small-cell predominant extranodal nasal-type natural killer/T-cell lymphoma (ENTNKT) of the orbit. METHODS: Retrospective chart review and histopathologic study with immunohistochemistry and in situ hybridization of 3 cases. RESULTS: Three cases of ENTNKT presented to the Mass Eye and Ear emergency room as orbital cellulitis over 1 year. The first case was unusual in that there was a predominance of small cells, giving the ENTNKT the histopathologic appearance of a nonmalignant inflammatory process. This challenging case is juxtaposed alongside 2 other cases, which exhibited the more typical lymphomatous microscopic appearance. DISCUSSION: ENTNKT can extend into the orbit from the adjacent sinuses or rarely arise primarily in the orbit. A diagnosis is typically made with a biopsy. Occasionally, however, the histopathologic diagnosis can be elusive when a predominance of small lymphomatous cells that are virtually indistinguishable from non-neoplastic inflammatory cells is present. Demonstration of CD56 positivity by immunostaining and in situ hybridization for Epstein-Barr virus are essential in confirming the diagnosis. CONCLUSIONS: ENTNKT should be considered both in the clinical and histopathologic differential diagnoses of orbital infections and idiopathic inflammations (pseudotumor).
Shanbhag SS, Chodosh J, Saeed HN. Sutureless amniotic membrane transplantation with cyanoacrylate glue for acute Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf 2019;Abstract
Amniotic membrane (AM) transplantation, when performed in the acute phase in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) for patients with ocular complications, is known to reduce the morbidity of ocular complications in the chronic phase. In conditions such as SJS/TEN, AM needs to be secured to the ocular surface as well as the eyelids. Previously, techniques of securing a large sheet of AM with fibrin glue to the ocular surface and with sutures and bolsters to the eyelids have been described in the acute phase of SJS/TEN. These techniques often necessitate the use of an operating room in acutely ill patients. We describe a bedside technique that uses cyanoacrylate glue to secure the AM to the eyelids, as well as long-term outcomes in 4 patients with acute SJS/TEN. The combination of a custom symblepharon ring to secure AM over the entire ocular surface and cyanoacrylate glue to secure AM to the eyelid margins is quick, painless, does not require local or general anesthesia, and might prove useful in other conditions previously shown to benefit from AMT, such as ocular chemical injuries.
Ing EB, Wang DN, Kirubarajan A, Benard-Seguin E, Ma J, Farmer JP, Belliveau MJ, Sholohov G, Torun N. Systematic Review of the Yield of Temporal Artery Biopsy for Suspected Giant Cell Arteritis. Neuroophthalmology 2019;43(1):18-25.Abstract
PURPOSE: To determine the positive yield (utility rate) of temporal artery biopsy (TAB) in patients with suspected giant cell arteritis (GCA). STUDY DESIGN: Systematic review (CRD42017078508) and meta-regression. MATERIALS AND METHODS: All articles concerning TAB for suspected GCA with English language abstracts from 1998 to 2017 were retrieved. Articles were excluded if they exclusively reported positive TAB, or only cases of known GCA. Where available, the pre-specified predictors of age, sex, vision symptoms, jaw claudication, duration of steroid treatment prior to TAB, specimen length, bilateral TAB, and use of ultrasound/MRI (imaging) were recorded for meta-regression. RESULTS: One hundred and thirteen articles met eligibility criteria. The was 92%, and with such high heterogeneity, meta-analysis is unsuitable. The median yield of TAB was 0.25 (95% confidence interval 0.21 to 0.27), with interquartile range 0.17 to 0.34. On univariate meta-regression age (coefficient 0.012,  = 0.025) was the only statistically significant patient factor associated with TAB yield. CONCLUSIONS: Systematic review revealed high heterogeneity in the yield of TAB. The median utility rate of 25% and its interquartile range provides a benchmark for decisions regarding the under/overutilization of TAB and aids in the evaluation of non-invasive alternatives for the investigation of GCA.
Chirapapaisan C, Abbouda A, Jamali A, Müller RT, Cavalcanti BM, Colon C, Witkin D, Sahin A, Dana R, Cruzat A, Hamrah P. In Vivo Confocal Microscopy Demonstrates Increased Immune Cell Densities in Corneal Graft Rejection Correlating With Signs and Symptoms. Am J Ophthalmol 2019;203:26-36.Abstract
PURPOSE: Diagnosis of graft rejection is based on patient symptoms and on clinical signs detected by slit-lamp biomicroscopy. This study investigated whether laser in vivo confocal microscopy (IVCM) can aid in the diagnosis of corneal graft rejection by detecting cellular corneal changes that take place after transplantation. DESIGN: Prospective case-control study. SUBJECTS: Thirty-eight eyes of 38 patients with penetrating keratoplasty (15 eyes with corneal graft rejection, 23 eyes without rejection) and 9 age-matched normal controls. METHODS: Laser IVCM was performed in the corneal grafts centrally. The density of immune cells (IC) was assessed for epithelial, sub-epithelial, stromal, and endothelial layers by 2 masked observers. IC density was compared among different groups and correlated to clinical signs and symptoms of corneal graft rejection. MAIN OUTCOME MEASUREMENTS: Outcome measurement was the IC density in the corneal layers and its associations with the presence of clinical signs and symptoms of corneal graft rejection. RESULTS: The IC density was significantly different between rejected and non-rejected grafts (P = 0.004) and different from that of normal controls (P = 0.001). Among corneal layers, IC density was significantly higher in rejected grafts than in non-rejected grafts in only the sub-basal (611.54 ± 573.74 vs. 340.61 ± 268.60 cells/mm, respectively; P = 0.049) and endothelial layers (250.62 ± 267.13 vs. 103.47 ± 81.91 cells/mm, respectively; P = 0.001). Patients with decreased best corrected visual acuity, Khodadoust line, and anterior chamber cells demonstrated a significant increase in total IC density (P < 0.05), whereas patients with symptoms of irritation, light sensitivity, and pain revealed a specific increase in IC density in the sub-basal layer (P < 0.05). Patients with ocular pain had higher IC density in the epithelial layer than those without pain (P = 0.03). CONCLUSIONS: Patients with corneal graft rejection demonstrate a significant increase in corneal immune cells, particularly, in the sub-basal and endothelial layers compared to patients with non-rejected grafts and controls. Although symptoms associated with endothelial rejection demonstrate a general increase in IC, pain, irritation, and light sensitivity are associated with increased IC in the sub-basal layer. Assessment of patients with corneal graft rejection by IVCM may serve as an adjunctive tool in the diagnosis and management of corneal graft rejection.
Zhao B, Torun N, Elsayed M, Cheng A-D, Brook A, Chang Y-M, Bhadelia RA. Diagnostic Utility of Optic Nerve Measurements with MRI in Patients with Optic Nerve Atrophy. AJNR Am J Neuroradiol 2019;40(3):558-561.Abstract
BACKGROUND AND PURPOSE: No MR imaging measurement criteria are available for the diagnosis of optic nerve atrophy. We determined a threshold optic nerve area on MR imaging that predicts a clinical diagnosis of optic nerve atrophy and assessed the relationship between optic nerve area and retinal nerve fiber layer thickness measured by optical coherence tomography, an ancillary test used to evaluate optic nerve disorders. MATERIALS AND METHODS: We evaluated 26 patients with suspected optic nerve atrophy (8 with unilateral, 13 with bilateral and 5 with suspected but not demonstrable optic nerve atrophy) who had both orbital MR imaging and optical coherence tomography examinations. Forty-five patients without optic nerve atrophy served as controls. Coronal inversion recovery images were used to measure optic nerve area on MR imaging. Retinal nerve fiber layer thickness was determined by optical coherence tomography. Individual eyes were treated separately; however, bootstrapping was used to account for clustering when appropriate. Correlation coefficients were used to evaluate relationships; receiver operating characteristic curves, to investigate predictive accuracy. RESULTS: There was a significant difference in optic nerve area between patients' affected eyes with optic nerve atrophy (mean, 3.09 ± 1.09 mm), patients' unaffected eyes (mean, 5.27 ± 1.39 mm; = .008), and control eyes (mean, 6.27 ± 2.64 mm; < .001). Optic nerve area ≤ 4.0 mm had a sensitivity of 0.85 and a specificity of 0.83 in predicting the diagnosis of optic nerve atrophy. A significant relationship was found between optic nerve area and retinal nerve fiber layer thickness ( = 0.68, < .001). CONCLUSIONS: MR imaging-measured optic nerve area ≤ 4.0 mm has moderately high sensitivity and specificity for predicting optic nerve atrophy, making it a potential diagnostic tool for radiologists.
Saeedi OJ, Elze T, D'Acunto L, Swamy R, Hegde V, Gupta S, Venjara A, Tsai J, Myers JS, Wellik SR, De Moraes CG, Pasquale LR, Shen LQ, Boland MV. Agreement and Predictors of Discordance of 6 Visual Field Progression Algorithms. Ophthalmology 2019;126(6):822-828.Abstract
PURPOSE: To determine the agreement of 6 established visual field (VF) progression algorithms in a large dataset of VFs from multiple institutions and to determine predictors of discordance among these algorithms. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Visual fields from 5 major eye care institutions in the United States were analyzed, including a subset of eyes with at least 5 Swedish interactive threshold algorithm standard 24-2 VFs that met our reliability criteria. Of a total of 831 240 VFs, a subset of 90 713 VFs from 13 156 eyes of 8499 patients met the inclusion criteria. METHODS: Six commonly used VF progression algorithms (mean deviation [MD] slope, VF index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort, and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen's κ coefficient. Bivariate and multivariate analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES: Agreement and discordance between algorithms. RESULTS: Individual algorithms showed poor to moderate agreement with each other when compared directly (κ range, 0.12-0.52). Based on at least 4 algorithms, 11.7% of eyes progressed. Major predictors of discordance or lack of agreement among algorithms were more depressed initial MD (P < 0.01) and older age at first available VF (P < 0.01). A greater number of VFs (P < 0.01), more years of follow-up (P < 0.01), and eye care institution (P = 0.03) also were associated with discordance. CONCLUSIONS: This extremely large comparative series demonstrated that existing algorithms have limited agreement and that agreement varies with clinical parameters, including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying big-data results to individual practices.

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