Efficiency, Precision, Validity, and Reliability of GlauCAT-Asian Computerized Adaptive Tests in Measuring Glaucoma-Related Quality of Life.

Purpose: To determine the efficiency, precision, and agreement of GlauCAT-Asian and its corresponding validity and reliability. Methods: In this cross-sectional study, 219 participants (mean ± standard deviation age, 66.59 ± 8.61 years; 34% female) across the spectrum of glaucoma severity and 50 glaucoma suspects were recruited from glaucoma clinics in Singapore. Participants answered seven computerized adaptive testing (CAT) evaluations (Ocular Comfort, Activity Limitation, Lighting, Mobility, Concerns, Psychosocial, Glaucoma Management) and underwent eye examinations. Efficiency (mean number of items required for each CAT and time taken for CAT versus full item banks [IBs]), agreement (concordance between CATs and full IB person measures, henceforth referred to as scores), and precision (standard error of measurement [SE]) were evaluated. Other validity and reliability metrics were also assessed. Results: The mean number of items administered ranged from 9 (Mobility/Glaucoma Management) to 12 (Ocular Comfort). Compared to answering the full IBs, CATs provided an average time saving of 38.3% (range, 10% to 70.6% for Lighting and Activity Limitation, respectively). Agreement between scores obtained by CAT versus full IB was high (intracorrelation coefficient ≥0.75), as was precision of score estimates (mean SE range: 0.35 for Psychosocial to 0.29 for Mobility). Scores from Activity Limitation, Mobility, Lighting, and Concerns decreased significantly as glaucoma severity increased (criterion validity; P-trend <0.05). All tests displayed good convergent/divergent validity and test-retest reliability. Conclusions: GlauCAT-Asian provides efficient, precise, accurate, valid, and reliable measurement of the patient-centered impact of glaucoma. Translational Relevance: GlauCAT-Asian may provide a valuable clinical tool for ophthalmologists to monitor impact of disease progression and the effectiveness of therapies.

Measuring glaucoma quality of life in an Asian population using item banking: psychometric evaluation and computerized adaptive testing simulations.

PURPOSE: To assess the psychometric properties of glaucoma-specific health-related quality of life (HRQoL) item banks (IBs), and explore their efficiency using computerized adaptive testing (CAT) simulations. METHODS: In this cross-sectional, clinical study, 300 Asian glaucoma patients answered 221 items within seven IBs: Ocular Comfort Symptoms (OS); Activity Limitation (AL); Lighting (LT); Mobility (MB); Glaucoma Management (GM); Psychosocial (PSY); and Work (WK). Rasch analysis was conducted to assess each IB's psychometric properties (e.g., item "fit" to the construct; unidimensionality) and a set of analytic performance criteria guiding decision making relating to retaining or dropping domains and items was employed. CAT simulations determined the mean number of items for 'high' and 'moderate' measurement precision (stopping rule: SEM 0.3 and 0.387, respectively). RESULTS: Participants' mean age was 67.2 ± 9.2 years (62% male; 87% Chinese). LT, MB, and GM displayed good psychometric properties overall. To optimize AL's psychometric properties, 16 items were deleted due to poor "fit", high missing data, item bias, low discrimination and/or a low clinical/patient importance rating. To resolve multidimensionality in PSY, we rehomed 16 items into a "Concern (CN)" domain. PSY and CN required further amendment, including collapsing of response categories, and removal of poorly functioning items (N = 7). Due to poor measurement precision, low applicability and high ceiling effect, low test information indices, and low item separation index the WK IB was not considered further. In CAT simulations on the final seven IBs (n = 182 items total), an average of 12.1 and 15.7 items per IB were required for moderate and high precision measurement, respectively. CONCLUSIONS: After reengineering our seven IBs, they displayed robust psychometric properties and good efficiency in CAT simulations. Once finalized, GlauCAT™-Asian may enable comprehensive assessment of the HRQoL impact of glaucoma and associated treatments.

Defining glaucomatous optic neuropathy using objective criteria from structural and functional testing.

BACKGROUND/AIMS: To identify objective criteria from optical coherence tomography (OCT) and perimetry that denote a useful, specific definition of glaucomatous optic neuropathy (GON) in eyes with open-angle glaucoma for comparisons among glaucoma research studies. METHODS: A cross-sectional study of adult patients with glaucoma from nine centres on five continents evaluated de-identified physician diagnosis, OCT and perimetry results for 2580 eyes (1531 patients) in an online database. Each eye was graded by their glaucoma specialist as either definite, probable or not GON. Objective measures from OCT and perimetry, derived from an online consensus panel comprising 176 glaucoma specialists globally, were compared against the three diagnostic levels. RESULTS: Diagnoses were 54% 'definite', 22% 'probable' and 24% 'not GON'. Using only OCT data or only field data had inadequate specificity (<90%). The best definitional choice for data from either the most recent or the preceding OCT/field pair had 77% sensitivity at 98% specificity and consisted of abnormal OCT superior or inferior nerve fibre layer quadrant with matching, opposite, abnormal Glaucoma Hemifield Test. CONCLUSIONS: Objective criteria to define GON are practical and may be useful for comparisons among clinical studies to supplement subjective clinical assessment.

Conventional Versus Accelerated Collagen Cross-Linking for Keratoconus: A Comparison of Visual, Refractive, Topographic and Biomechanical Outcomes.

OBJECTIVE: The aim was to compare the visual, refractive, topographic and biomechanical outcomes in patients with progressive keratoconus treated with either conventional or accelerated crosslinking at one year follow up. METHODS: It is a prospective, non-randomised interventional study of 76 patients who underwent conventional (CXL; 3mW/cm2 for 30 minutes) or accelerated cross linking (KXL; 30mW/cm2 for 4 minutes) for progressive keratoconus. Baseline and postoperative visual acuity, manifest refraction, corneal topography, pachymetry, endothelial cell density and biomechanical parameters of corneal hysteresis and corneal resistance factor were evaluated and compared. RESULTS: The 2 groups were comparable in terms of uncorrected and best corrected visual acuity and spherical equivalent. Both groups showed no significant increase in K1, K2 and Kmean from baseline at 12 months. There was also no difference between the CXL and KXL group for postoperative corneal topography as well as central and minimal pachymetry up to 12 months. There was a significant increase in both corneal hysteresis (0.62mm Hg, P=0.04) and corneal resistance factor (0.91mm Hg, P=0.003) in the KXL group at 12 months but not in the CXL group. There was no significant endothelial cell loss throughout follow up in both the groups. CONCLUSION: We have established comparability of the 2 protocols in stabilizing the progression of keratoconus. Our findings also suggested an added biomechanical advantage of accelerated crosslinking at 1 year follow up.

Ocular lubricant use in medically and surgically treated glaucoma: a retrospective longitudinal analysis.

BACKGROUND: Chronic use of intraocular pressure-lowering medications is associated with ocular surface disease (OSD). In this study, we assess the incidence of topical lubricant use as a surrogate marker for underlying OSD, in medically and surgically treated glaucoma patients. METHODS: Retrospective chart review was performed for newly diagnosed glaucoma patients who were started on topical medications in 2007 and followed up over a 5-year period. Primary outcome measure was the incidence of topical lubricant use in these patients and a subset of these patients who required glaucoma or cataract surgery during follow-up. RESULTS: Charts of 505 newly diagnosed glaucoma patients with no prior history of ocular lubricant use were analyzed. Mean age was 63.9 years (SD 11.1), 42.8% were women. One hundred one (20.0%) patients underwent phacoemulsification surgery, 80 underwent mitomycin C (MMC) augmented phacotrabeculectomy, 16 underwent MMC-augmented trabeculectomy and 3 underwent tube surgery during the course of follow-up as their only type of surgery. Five-year incidence of lubricant use was 59% in all glaucoma subjects; 54.1% of patients were on medical treatment and 74.0% of patients who underwent phacotrabeculectomy or trabeculectomy were started on lubricants, respectively (P=0.0011); 60.4% of glaucoma subjects who underwent phacoemulsification surgery were started on lubricants. Incidence of lubricant use increased from 17.7% preoperatively to 74.0% postoperatively in subjects who required trabeculectomy or phacotrabeculectomy. Incidence of lubricant use was similar in patients on one or multiple glaucoma medications, with the mean onset of lubricant use being 10 months after starting glaucoma medication in both groups. Females were more likely to use artificial tears compared with males (P=0.002). CONCLUSION: Both medical and surgical management of glaucoma have an adverse effect on the ocular surface. Chronic use of glaucoma medications was associated with a high incidence of ocular lubricant use. MMC-augmented trabeculectomy was associated with an even higher incidence of ocular lubricant use.

Dataset of aqueous humor cytokine profile in HIV patients with Cytomegalovirus (CMV) retinitis.

The data shows the aqueous humor cytokine profiling results acquired in a small cohort of 17 HIV patients clinically diagnosed with Cytomegalovirus retinitis using the FlexMAP 3D (Luminex®) platform using the Milliplex Human Cytokine® kit. Aqueous humor samples were collected from these patients at different time points (pre-treatment and at 4-weekly intervals through the 12-week course of intravitreal ganciclovir treatment) and 41 cytokine levels were analyzed at each time point. CMV DNA viral load was assessed in 8 patients at different time points throughout the course of ganciclovir treatment. The data described herein is related to the research article entitled "Aqueous humor immune factors and cytomegalovirus (CMV) levels in CMV retinitis through treatment - The CRIGSS study" (Iyer et al., 2016) [1]. Cytokine levels against the different time points which indicate the response to the given treatment and against the CMV viral load were analyzed.

Aqueous humor immune factors and cytomegalovirus (CMV) levels in CMV retinitis through treatment - The CRIGSS study.

PURPOSE: This study aims to perform comprehensive longitudinal immune factor analysis of aqueous humor in relation to the aqueous CMV viral load and systemic CD4 counts during treatment of patients with co-infection of HIV and CMVR. METHODS: Aqueous humor samples were collected from 17 HIV-positive patients with CMVR scheduled to undergo weekly intravitreal ganciclovir therapy as part of the prospective CMV Retinitis Intravitreal Ganciclovir Singapore Study (CRIGSS) over the course of 1year. Full data across all the 4 time points was obtained and analyzed for CMV DNA viral load, 41 cytokine and chemokine factors using real-time PCR with the FlexMAP 3D (Luminex®) platform and assessed using the Milliplex Human Cytokine® kit. RESULTS: The following immune factors (Spearman correlation coefficient r value in parenthesis, p<0.05) showed strong correlation with CMV DNA load in the aqueous - MCP-1 (0.80, IFN-g (0.83), IP-10 (0.82), IL-8 (0.81), fractalkine (0.73), RANTES (0.68) - while the following showed moderate correlation - PDGF-AA (0.58), Flt-3L (0.59) and G-CSF (0.53). Only PDGF-AA revealed a statistically significant negative correlation with serum CD4 levels (r=-0.74). CONCLUSION: Immune factors that correlate with intraocular CMV DNA load are identified. They are indicative of a Th1 and monocyte-macrophage mediated response, and exhibit a decreasing trend longitudinally through the course of treatment. These factors may be an important new consideration in individualizing the treatment of patients with CMVR.

Cytokine analysis of aqueous humor in HIV patients with cytomegalovirus retinitis.

PURPOSE: Cytomegalovirus retinitis (CMVR) is the most common opportunistic ocular infection in patients with AIDS. Comprehensive analysis of aqueous humor for immunologic factors has yet to be performed in patients with CMVR. This study aims to perform comprehensive immune factor analysis of aqueous humor in CMVR patients to determine the presence of any characteristic immunological profile in the aqueous humor. METHODS: Comparative prospective analysis of aqueous humor was performed across three groups: (1) AIDS patients with CMVR (CMVR group) (n=20), (2) HIV-positive patients without CMVR (HIV group) (n=6) and (3) patients undergoing cataract surgery with no underlying ocular infection or inflammation (control group) (n=11). At least 100µl of aqueous humor was drawn from all subjects and fractionated prior to analysis for 41 cytokines, chemokines and growth factors with the FlexMAP 3D (Luminex®) platform using the Milliplex Human Cytokine® kit. RESULTS: Three distinct immunologic signatures were observed in the aqueous humor of the three groups. Statistically significant differences (p<0.05) were observed across the three groups with the HIV group having lower levels and CMVR group having raised levels for the following factors: IP-10, fractalkine, PDGF-AA, G-CSF, Flt-3L and MCP-1. CONCLUSION: Aqueous humor though clinically quiescent in CMVR revealed a unique immunologic signature consistent with a combined Th-1 and monocyte-macrophage mediated response. Subsequent longitudinal analysis of aqueous cytokine levels of CMVR through the course of treatment would allow better understanding of the immunopathogenetic mechanisms of CMVR. This may also be used to better prognosticate the disease, predict complications and allow better assessment of treatment response and individualization of treatment in the future.

Clinical profile, management, and outcome of retinoblastoma in singapore.

PURPOSE: To analyze the clinical manifestations and treatment outcomes for patients with retinoblastoma in Singapore from 1997 to 2010. METHODS: Medical records of 51 patients (67 eyes) diagnosed as having retinoblastoma were analyzed. Data on laterality, genetics, presentation, disease severity, treatment, and prognosis were collected. RESULTS: The mean age of presentation was 25.7 ± 19.9 months. Sixteen (31.4%) of the patients had bilateral disease, of whom 2 had an associated pineal tumor. Leukocoria was the most common sign. Two had metastasis at diagnosis. Only 3 patients (5.9%) had a family history. Using the International Intraocular Retinoblastoma Classification, 6.0% were Group A, 6.0% were Group B, 3.0% were Group C, 38.8% were Group D, and 49.2% were Group E. Chemotherapy and focal therapy were administered for 4 of 35 (12.9%) patients with unilateral retinoblastoma (50% had successful globe preservation) and 13 of 16 (81.3%) patients with bilateral retinoblastoma (42.3% had successful globe preservation). Overall, globe preservation was achieved in 100% of Groups A, B, and C, and 23.1% of Group D cases. The 5-year survival rate overall, for unilateral retinoblastoma, and for bilateral retinoblastoma was 91%, 97%, and 76% respectively. CONCLUSION: The overall 5-year survival rate is comparable to international data in most developed countries. However, most patients presented with advanced disease, making the rate of globe preservation lower than in some developed countries. Better education of the public and healthcare professionals may increase awareness and enable early detection of the disease.