Diagnostic Accuracy of Frequency-Doubling Technology and the Moorfields Motion Displacement Test for Glaucoma.

PURPOSE: Portable perimetric testing could be useful for community-based glaucoma screening programs. Frequency-doubling technology (FDT) and the Moorfields motion displacement test (MDT) are portable perimeters that have shown promise as potential screening tools for glaucoma. This study's goal was to determine the diagnostic accuracy of FDT and MDT for visual field defects and glaucoma. DESIGN: Prospective, cross-sectional, diagnostic accuracy study. PARTICIPANTS: A consecutive series of patients aged ≥ 50 years who presented to a glaucoma clinic in South India and had never undergone Humphrey field analyzer (HFA) visual field testing in the past. METHODS: Participants underwent 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard HFA perimetry, FDT perimetry, MDT perimetry, and iPad perimetry using visualFields Easy in random order. Ophthalmologist grades of HFA and optic nerve head photographs were used as reference standards for glaucoma and field defect presence. Receiver operating characteristic curves were constructed to assess the diagnostic accuracy of various parameters for each test. MAIN OUTCOME MEASURES: Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). RESULTS: Overall, 292 eyes from 173 participants were included, with 112 eyes classified as moderate or worse glaucoma. For moderate or worse glaucoma detection, the best parameter on FDT was mean deviation (MD) (AUROC, 0.84; 95% confidence interval [CI], 0.79-0.89) and the best parameter on MDT was global probability of true damage (GPTD) (AUROC, 0.87; 95% CI, 0.82-0.91). When specificity was set to 90%, the sensitivity for detection of moderate or worse glaucoma was 55% (95% CI, 39%-68%) for FDT MD and 62% (95% CI 52%-71%) for MDT GPTD. CONCLUSIONS: Frequency-doubling technology and MDT perimetry had fair diagnostic accuracy for glaucoma detection when administered to naïve test takers in this South Indian population. Although not appropriate for use as a sole glaucoma screening test, these perimetric tests may be useful as ancillary tests. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Diagnostic accuracy of an iPad application for detection of visual field defects.

BACKGROUND/OBJECTIVES: Tablet-based perimetry could be used to test for glaucomatous visual field defects in settings without easy access to perimeters, although few studies have assessed diagnostic accuracy of tablet-based tests. The goal of this study was to determine the diagnostic accuracy of iPad perimetry using the visualFields Easy application. SUBJECTS/METHODS: This was a prospective, cross-sectional study of patients undergoing their first Humphrey Field Analyser (HFA) visual field test at a glaucoma clinic in India. Participants underwent 24-2 SITA Standard HFA testing and iPad-based perimetry with the visualFields Easy application. Reference standards for both visual field loss and suspected glaucoma were determined by ophthalmologist review of HFA results and optic disc photographs. Receiver operating characteristic curves were constructed to assess diagnostic accuracy at various test thresholds. RESULTS: 203 eyes from 115 participants were included, with 82 eyes classified as moderate or worse glaucoma. iPad perimetry had an area under the receiver operating characteristic (AUROC) curve of 0.64 (95% CI 0.57 to 0.71) for detection of any visual field defect relative to HFA and an AUROC of 0.68 (0.59 to 0.76) for detection of moderate or worse glaucoma relative to ophthalmologist examination. At a set specificity of 90%, the sensitivity of iPad perimetry for detection of moderate or worse glaucoma was 35% (22-48%). CONCLUSIONS: iPad perimetry using the visualFields Easy application had inadequate diagnostic accuracy to be used as a screening tool for glaucoma in this South Indian population.

Ocular Surface Immune Cell Profiles in Contact Lens-Induced Discomfort.

Purpose: Contact lens-induced discomfort (CLD) remains a primary factor in discontinuation or prevention of contact lens wear. Thus, we investigated the role of ocular surface immune cells in subjects with CLD. Methods: Habitual contact lens (CL) wearers with CLD (n = 19; 38 eyes) and without CLD (n = 21; 42 eyes) as determined by the Contact Lens Dry Eye Questionnaire-8 was included in a trial. Enrolled subjects used either of the two types of CL (designated as CL-A or CL-D). Ocular surface cells from the bulbar conjunctiva were obtained by impression cytology. The collected cells were phenotyped using fluorochrome-conjugated antibodies specific for leukocytes (CD45+), neutrophils (CD66b+,High,Low), macrophages (CD163+), T cells (CD3+CD4+, CD3+CD8+), natural killer (NK) cells (CD56+, High, Low), natural killer T (NKT) cells (CD3+CD56+), and gamma delta T (γδT) cells (CD3+γδTCR+) by flow cytometry. Further, corneal dendritic cell density (cDCD) was also determined using in vivo confocal microscopy. Results: Significantly higher proportions of CD45+ cells were observed in subjects with CLD compared to those without CLD. The percentages of CD66bTotal,Low, CD163+, pan T cells, CD4+T cells, CD8+T cells, CD56Total,High,Low (NK) cells, and NKT cells, as well as the CD4/CD8 ratio, were significantly higher in CLD subjects. The proportion of T cells (CD4, CD8, CD4/CD8 ratio, NKT cells) and macrophages exhibited a direct association with discomfort score. The percentages of CD45+, CD66bTotal,Low, CD163+, CD3+, CD56Total,High,Low, and NKT cells and cDCD were significantly higher in CLD subjects wearing CL-D. The percentages of CD66bHigh, CD4+T cells, CD8+T cells, NKT cells, and CD4/CD8 ratio were significantly higher in CLD subjects wearing CL-A. Conclusions: Increased proportions of ocular surface immune cells are observed in CLD, and the lens type could impact the immune cells associated with CLD. Translational Relevance: The association between the proportion of altered ocular surface immune cell subsets and contact lens-induced discomfort underpins the importance of considering immune-related aspects during contact lens development and in the clinical management of ocular surface pain.

Deep Learning for Glaucoma Detection and Identification of Novel Diagnostic Areas in Diverse Real-World Datasets.

Purpose: To develop a three-dimensional (3D) deep learning algorithm to detect glaucoma using spectral-domain optical coherence tomography (SD-OCT) optic nerve head (ONH) cube scans and validate its performance on ethnically diverse real-world datasets and on cropped ONH scans. Methods: In total, 2461 Cirrus SD-OCT ONH scans of 1012 eyes were obtained from the Glaucoma Clinic Imaging Database at the Byers Eye Institute, Stanford University, from March 2010 to December 2017. A 3D deep neural network was trained and tested on this unique raw OCT cube dataset to identify a multimodal definition of glaucoma excluding other concomitant retinal disease and optic neuropathies. A total of 1022 scans of 363 glaucomatous eyes (207 patients) and 542 scans of 291 normal eyes (167 patients) from Stanford were included in training, and 142 scans of 48 glaucomatous eyes (27 patients) and 61 scans of 39 normal eyes (23 patients) were included in the validation set. A total of 3371 scans (Cirrus SD-OCT) from four different countries were used for evaluation of the model: the non overlapping test dataset from Stanford (USA) consisted of 694 scans: 241 scans from 113 normal eyes of 66 patients and 453 scans of 157 glaucomatous eyes of 89 patients. The datasets from Hong Kong (total of 1625 scans; 666 OCT scans from 196 normal eyes of 99 patients and 959 scans of 277 glaucomatous eyes of 155 patients), India (total of 672 scans; 211 scans from 147 normal eyes of 98 patients and 461 scans from 171 glaucomatous eyes of 101 patients), and Nepal (total of 380 scans; 158 scans from 143 normal eyes of 89 patients and 222 scans from 174 glaucomatous eyes of 109 patients) were used for external evaluation. The performance of the model was then evaluated on manually cropped scans from Stanford using a new algorithm called DiagFind. The ONH region was cropped by identifying the appropriate zone of the image in the expected location relative to Bruch's Membrane Opening (BMO) using a commercially available imaging software. Subgroup analyses were performed in groups stratified by eyes, myopia severity of glaucoma, and on a set of glaucoma cases without field defects. Saliency maps were generated to highlight the areas the model used to make a prediction. The model's performance was compared to that of a glaucoma specialist using all available information on a subset of cases. Results: The 3D deep learning system achieved area under the curve (AUC) values of 0.91 (95% CI, 0.90-0.92), 0.80 (95% CI, 0.78-0.82), 0.94 (95% CI, 0.93-0.96), and 0.87 (95% CI, 0.85-0.90) on Stanford, Hong Kong, India, and Nepal datasets, respectively, to detect perimetric glaucoma and AUC values of 0.99 (95% CI, 0.97-1.00), 0.96 (95% CI, 0.93-1.00), and 0.92 (95% CI, 0.89-0.95) on severe, moderate, and mild myopia cases, respectively, and an AUC of 0.77 on cropped scans. The model achieved an AUC value of 0.92 (95% CI, 0.90-0.93) versus that of the human grader with an AUC value of 0.91 on the same subset of scans (\(P=0.99\)). The performance of the model in terms of recall on glaucoma cases without field defects was found to be 0.76 (0.68-0.85). Saliency maps highlighted the lamina cribrosa in glaucomatous eyes versus superficial retina in normal eyes as the regions associated with classification. Conclusions: A 3D convolutional neural network (CNN) trained on SD-OCT ONH cubes can distinguish glaucoma from normal cases in diverse datasets obtained from four different countries. The model trained on additional random cropping data augmentation performed reasonably on manually cropped scans, indicating the importance of lamina cribrosa in glaucoma detection. Translational Relevance: A 3D CNN trained on SD-OCT ONH cubes was developed to detect glaucoma in diverse datasets obtained from four different countries and on cropped scans. The model identified lamina cribrosa as the region associated with glaucoma detection.

Comparison of Structural, Functional, Tonometric, and Visual Acuity Testing for Glaucoma: A Prospective Diagnostic Accuracy Study.

PURPOSE: To determine the diagnostic accuracy of potential screening tests for moderate to advanced glaucoma. DESIGN: Prospective diagnostic test accuracy study. PARTICIPANTS: The study enrolled a consecutive series of patients aged ≥50 years who presented to a glaucoma clinic in South India without ever having received automated visual field testing. METHODS: All participants underwent 8 index tests: OCT of the peripapillary retinal nerve fiber layer, optic disc photography, Moorfield's Motion Displacement Test (MDT), frequency doubling technique perimetry, noncontact tonometry, pneumatonometry, presenting visual acuity, and best-corrected visual acuity. Participants also underwent stereoscopic photographs and Humphrey visual fields, which were used by 2 ophthalmologists to arrive at the reference standard diagnosis of moderate to advanced glaucoma. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. RESULTS: A total of 217 people were enrolled; 321 eyes from 180 participants had all tests performed. Of these, 127 eyes (40%) were classified as having moderate to advanced glaucoma. Among the 8 tests, OCT best optimized sensitivity (84%, 95% confidence interval [CI], 76-90) and specificity (75%, 95% CI, 68-81). Moorfield's Motion Displacement Test was the best perimetric test, with a sensitivity of 91% (95% CI, 85-96) and specificity of 53% (95% CI, 44-61). Pressure and vision tests were not sensitive (e.g., sensitivity of 16%, 95% CI, 9-23 for noncontact tonometry and 23%, 95% CI, 15-31 for best-corrected visual acuity). Moorfield's Motion Displacement Test identified 16 of 127 eyes (13%) with glaucoma that were not captured by OCT, but also had false-positive results in 65 of 194 eyes (34%) without glaucoma that OCT correctly classified as negative. CONCLUSIONS: OCT had moderate sensitivity and fair specificity for diagnosing moderate to advanced glaucoma and should be prioritized during an initial assessment for glaucoma.

Accuracy of autorefraction in an adult Indian population.

PURPOSE: Autorefractors allow non-specialists to quickly assess refractive error, and thus could be a useful component of large-scale vision screening programs. In order to better characterize the role of autorefraction for public health outreach programs in resource-limited settings, the diagnostic accuracy of two autorefractors was assessed relative to subjective refraction in an adult Indian population. METHODS: An optometrist refracted a series of patients aged ≥50 years at an eye clinic in Bangalore, India using the Nidek ARK-900 autorefractor first, followed by the 3nethra Royal autorefractor, and then subjective refraction. The diagnostic accuracy of each autorefractor for myopia, hyperopia, and astigmatism was assessed using subjective refraction as the reference standard, and measures of agreement between refractions were calculated. RESULTS: A total of 197 eyes in 104 individuals (mean age 63 ± 8 years, 52% female) were evaluated. Both autorefractors produced spherical equivalent estimates that were on average more hyperopic than subjective refraction, with a measurement bias of +0.16 D (95%CI +0.09 to +0.23D) for Nidek and +0.42 D (95%CI +0.28 to +0.54D) for 3nethra. When comparing pairs of measurements from autorefraction and subjective refraction, the limits of agreement were approximately ±1D for the Nidek autorefractor and ±1.75D for the 3Nethra autorefractor. The sensitivity and specificity of detecting ≥1 diopter of myopia were 94.6% (95%CI 86.8-100%) and 92.5% (95%CI 88.9-97.5%) for the Nidek, and 89.2% (95%CI 66.7-97.4) and 77.5% (95%CI 71.2-99.4%) for the 3Nethra. The accuracy of each autorefractor increased at greater levels of refractive error. CONCLUSIONS: The sensitivity and specificity of the Nidek autorefractor for diagnosing refractive error among adults ≥50 years in an urban Indian clinic was sufficient for screening for visually significant refractive errors, although the relatively wide limits of agreement suggest that subjective refinement of the eyeglasses prescription would still be necessary.

A 3D Deep Learning System for Detecting Referable Glaucoma Using Full OCT Macular Cube Scans.

Purpose: The purpose of this study was to develop a 3D deep learning system from spectral domain optical coherence tomography (SD-OCT) macular cubes to differentiate between referable and nonreferable cases for glaucoma applied to real-world datasets to understand how this would affect the performance. Methods: There were 2805 Cirrus optical coherence tomography (OCT) macula volumes (Macula protocol 512 × 128) of 1095 eyes from 586 patients at a single site that were used to train a fully 3D convolutional neural network (CNN). Referable glaucoma included true glaucoma, pre-perimetric glaucoma, and high-risk suspects, based on qualitative fundus photographs, visual fields, OCT reports, and clinical examinations, including intraocular pressure (IOP) and treatment history as the binary (two class) ground truth. The curated real-world dataset did not include eyes with retinal disease or nonglaucomatous optic neuropathies. The cubes were first homogenized using layer segmentation with the Orion Software (Voxeleron) to achieve standardization. The algorithm was tested on two separate external validation sets from different glaucoma studies, comprised of Cirrus macular cube scans of 505 and 336 eyes, respectively. Results: The area under the receiver operating characteristic (AUROC) curve for the development dataset for distinguishing referable glaucoma was 0.88 for our CNN using homogenization, 0.82 without homogenization, and 0.81 for a CNN architecture from the existing literature. For the external validation datasets, which had different glaucoma definitions, the AUCs were 0.78 and 0.95, respectively. The performance of the model across myopia severity distribution has been assessed in the dataset from the United States and was found to have an AUC of 0.85, 0.92, and 0.95 in the severe, moderate, and mild myopia, respectively. Conclusions: A 3D deep learning algorithm trained on macular OCT volumes without retinal disease to detect referable glaucoma performs better with retinal segmentation preprocessing and performs reasonably well across all levels of myopia. Translational Relevance: Interpretation of OCT macula volumes based on normative data color distributions is highly influenced by population demographics and characteristics, such as refractive error, as well as the size of the normative database. Referable glaucoma, in this study, was chosen to include cases that should be seen by a specialist. This study is unique because it uses multimodal patient data for the glaucoma definition, and includes all severities of myopia as well as validates the algorithm with international data to understand generalizability potential.

Reproducibility of 5 Methods of Ocular Tonometry.

PURPOSE: To evaluate the agreement between Goldmann applanation tonometry (GAT; Haag-Streit, Bern, Switzerland) and several portable tonometers that could be used for glaucoma screening programs. DESIGN: Evaluation of a diagnostic test. PARTICIPANTS: Three hundred twenty-one eyes of 168 participants seeking treatment at the glaucoma clinic of a tertiary eye hospital in India. METHODS: Participants underwent intraocular pressure (IOP) measurement with GAT and 4 index tests: the Icare TA01i rebound tonometer (Icare USA, Raleigh, NC), a noncontact tonometer (NCT; Topcon CT-80; Topcon; Tokyo, Japan), a pneumatonometer (Model 30; Reichert Technologies; Depew, NY), and the Tono-Pen AVIA (Reichert Technologies). MAIN OUTCOME MEASURES: Estimates of reproducibility of IOP measurements between each index test and GAT, including the intraclass correlation coefficient (ICC) and the Bland-Altman 95% limits of agreement. RESULTS: The Icare showed the greatest agreement with GAT (ICC, 0.69; 95% confidence interval, 0.61-0.74), followed by the NCT (ICC, 0.65; 95% confidence interval, 0.58-0.71), the Tono-Pen (ICC, 0.51; 95% confidence interval, 0.43-0.59), and the pneumatonometer (ICC, 0.36; 95% confidence interval, 0.27-0.44). The pneumatonometer and Tono-Pen tended to overestimate IOP relative to GAT, with a mean difference of 3.4 mmHg (95% limits of agreement [LOA], -7.3 to 14.1 mmHg) for the pneumatonometer and 3.2 mmHg (95% LOA, -6.1 to 12.6 mmHg) for the Tono-Pen. In contrast, measurements from the Icare and NCT were on average within 1 point of those for GAT (mean difference, -0.4 mmHg [95% LOA, -8.4 to 7.6 mmHg] and -0.5 mmHg [95% LOA, -8.7 to 7.6 mmHg], respectively). CONCLUSIONS: The Icare and NCT both demonstrated good agreement with GAT across a wide range of IOPs and could be considered for glaucoma screening programs.

Use of Wavefront Imaging Technology to Demonstrate Improvement in Corneal Aberrations Using Piggyback Contact Lens in a Keratoconus Eye With Intrastromal Corneal Ring Segment Implantation: A Case Report.

OBJECTIVE: To quantify short-term changes in corneal high-order aberrations (HOA) with piggyback contact lens use in an eye with keratoconus that had undergone intrastromal ring segment (Intacs) implantation. METHODS: A patient with keratoconus reporting of distorted images after Intacs surgery was found to have HOA (trefoil, point spread function [PSF], and modulation transfer function [MTF]) as measured using wavefront technology (Nidek OPD-Scan III) and evidenced by her cylindrical correction. She underwent piggyback contact lens (silicone hydrogel and fluoroperm rigid gas-permeable lenses) fitting in an attempt to improve the HOA. RESULTS: After piggyback contact lens fitting, her visual acuity improved and all her visual symptoms resolved. High-order aberrations reduced from 3.152 to 0.490 after the lens fitting and was noted to be 0.447 at 6 months; trefoil also significantly improved (0.360-0.096; it was 0.031 at 6 months). The cylinder decreased from -4.50 to -0.75 and was stable at 6 months (-1.00). There was also significant improvement in PSF and MTF. CONCLUSIONS: Visual acuity and symptoms along with HOA and cylinder improved after fitting of piggyback contact lens in our patient with keratoconus who had undergone Intacs.

Comparison of intraocular pressure measurement with Scheimpflug-based noncontact tonometer with and without hydrogel contact lenses.

OBJECTIVES: The objective was to determine the repeatability of intraocular pressure (IOP) measurements made through a soft contact lens (CL) using the Scheimpflug noncontact tonometry in healthy subjects. METHODS: This prospective, randomized, single-center study included one eye of 88 subjects (40 male and 48 female). Only participants without glaucoma or any other ocular pathology were included in this study. Three consecutive IOP measurements by the Scheimpflug noncontact tonometry were performed with and without daily disposable hydrogel CLs (-0.50 DS) (Dailies-nelfilcon A, 69% water, 8.7 mm base curve, 14 mm diameter, center thickness 0.10 mm) by a single operator. To avoid any bias arising from diurnal variation, all measurements were made at a similar time of day (11 am ± 1 h). The repeatability of IOP measurements using the Scheimpflug noncontact tonometry with and without CLs was evaluated using Pearson's correlation analysis. Bland-Altman plotting was used to assess the limits of agreement between the measurements with and without CLs. RESULTS: The mean (± standard deviation) IOPs with and without CL were 13.80 ± 2.70 and 13.79 ± 2.54 mm of Hg respectively. The mean difference was 0.01 ± 0.16 (95% confidence interval, +1.97 to - 2.00) mm Hg. Statistical analysis via paired t-test showed no statistical difference between the two groups with (P = 0.15). A good correlation was found for IOP measurements with and without CL (r = 0.93, P < 0.001). Good test-retest reliability was found when IOP was measured with and without CL. CONCLUSION: There was no significant difference between IOP measured with and without CLs by Scheimpflug noncontact tonometry.

Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A.

PURPOSE: The present study was designed to understand the role of inflammatory cytokines secreted by corneal epithelial cells in keratoconus (KC) and the response to treatment with cyclosporine A (CyA). METHODS: The study involved 129 Indian KC patients clinically graded according to Amsler-Krumeich classification and 20 healthy, nonectatic subjects as controls. Tear levels of matrix metalloproteinase-9 (MMP9), interleukin-6 (IL6), and tumor necrosis factor-α (TNFα) were measured using ELISA kits. Gene expression was measured by qPCR in corneal epithelial cells obtained by debridement from subjects undergoing ocular surface surgeries. In addition, epithelial cells were stimulated with TNFα and treated with CyA to study its role on MMP9 expression. Finally, 20 KC patients (27 eyes) with inflammatory symptoms were treated with topical CyA application. RESULTS: We observed that MMP9, TNFα, and IL6 levels were strongly upregulated at the mRNA level in KC patient epithelia. Similarly, tears collected from KC patients exhibited high levels of MMP9 and IL6 protein. Cyclosporine A treatment significantly reduced the mRNA expression levels of IL6 and TNFα in both short- and long-term treatments; however, it reduced MMP9 levels only in long-term treatment in cultured corneal epithelial cells. Subsequent treatment of KC patients with CyA for approximately 6 months reduced tear MMP9 levels and led to local reduction in corneal curvatures as determined by corneal topography maps. CONCLUSIONS: The data indicate that corneal epithelium contributes to elevated MMP9 and inflammatory cytokine expression in tears of KC patients. Cyclosporine A treatment reduced MMP9 and inflammatory cytokine levels in an in vitro inflammation model system. In KC patients, CyA treatment reduced MMP9 levels measured in tears with concomitant arrest of disease progression. Therefore, CyA might be a novel treatment strategy in KC patients but requires additional evaluation in larger cohorts. (ClinicalTrials.gov number, NCT01746823.).

Association between genetic variants in the base excision repair pathway and outcomes after hematopoietic cell transplantations.

Alkylating agents with or without ionizing radiation are frequently used in pretransplant conditioning regimens. Damage induced by these agents is commonly repaired by the base excision repair (BER) pathway. Hence, we hypothesized that genetic polymorphisms in the BER pathway will be associated with posthematopoietic cell transplant (HCT) outcomes. We evaluated the association between single nucleotide polymorphisms (SNPs) (n = 179) in the BER pathway with treatment-related mortality (TRM) at 1 year and disease relapse in a cohort of 470 recipients who underwent allogeneic HCT for treatment of hematologic malignancies at the University of Minnesota. After adjustment for age at transplant, donor type, race, and conditioning regimen, 4 SNPs in OGGI, LIG3, and MUTYH genes (rs159153, rs3135974, rs3219463, and rs3219476) were associated with increased risk of TRM, whereas 2 SNPs in the TDG gene (rs167715 and rs2374327) were associated with decreased risk of TRM at 1 year (P or=4 deleterious alleles versus 14% for

Chronic graft-versus-host disease (cGVHD) following unrelated donor hematopoietic stem cell transplantation (HSCT): higher response rate in recipients of unrelated donor (URD) umbilical cord blood (UCB).

We present a comparative analysis of clinical presentation and response to treatment in 170 patients with chronic graft versus host disease (cGVHD) (123 following transplant from an unrelated donor [URD] and 47 from umbilical cord blood [UCB]). URD transplant recipients were significantly younger (median age 25 versus 39 years, P = .002; and the donor grafts were mostly HLA matched (67% versus 10%, P < .0001). UCB recipients had more frequent responses (complete remission [CR] + partial remission [PR]) to treatment (URD 48% versus UCB 74% at 2 months [P = .005]; 49% versus 78% at 6 months [P = .001] and 51% versus 72% at 1 year [P = .03] in the URD and UCB groups, respectively). Nonrelapse mortality (NRM) after diagnosis of cGVHD was worse after URD grafts. (1 year NRM 27% [19%-35%] URD versus 11% [2%-20%] UCB, P = .055). Separate multivariate analyses were performed in each cohort. In both, thrombocytopenia and no CR or PR at 2 months were independently associated with increased mortality. In addition, progressive onset of cGVHD was a significant predictor of increased mortality in URD cohort. These data suggest that cGVHD following UCB transplant may be more responsive to therapy and also lead to a lower NRM.