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.

Endothelial cell loss associated with minimally invasive glaucoma surgery.

PURPOSE OF REVIEW: Minimally invasive glaucoma surgery (MIGS) represents a safer, albeit moderately effective surgical option for intraocular pressure control. However, the CyPass Micro-Stent (Alcon Laboratories) was withdrawn from the market in 2018 as the COMPASS-XT study demonstrated greater cornea endothelial cell (CEC) loss in patients who received the CyPass Micro-Stent with phacoemulsification compared with phacoemulsification alone. This led to the increased attention on MIGS-associated CEC loss and thus, this review will summarise the recent, available evidence on MIGS-associated CEC loss. RECENT FINDINGS: Prospective clinical trials and retrospective observational studies published between 2011 and 2021 reported a wide range of 12 month CEC loss from 'insignificant', and up to 14.6%, for phacoemulsification combined with various MIGS procedures. Recent clinical trials over the same time period reported CEC loss of 12.8-15.2% associated with phacoemulsification alone. SUMMARY: Apart from the CyPass Micro-Stent clinical trial, no other studies on combined phacoemulsification with MIGS that is 'phaco-plus' procedures have reported a higher short-term CEC loss compared with phacoemulsification alone. However, studies that specifically examine postprocedural CEC loss following phacoemulsification compared to 'phaco-plus' procedures over a longer follow-up period are required.

Glaucoma screening: where are we and where do we need to go?

PURPOSE OF REVIEW: Current recommendations for glaucoma screening are decidedly neutral. No studies have yet documented improved long-term outcomes for individuals who undergo glaucoma screening versus those who do not. Given the long duration that would be required to detect a benefit, future studies that may answer this question definitively are unlikely. Nevertheless, advances in artificial intelligence and telemedicine will lead to more effective screening at lower cost. With these new technologies, additional research is needed to determine the costs and benefits of screening for glaucoma. RECENT FINDINGS: Using optic disc photographs and/or optical coherence tomography, deep learning systems appear capable of diagnosing glaucoma more accurately than human graders. Eliminating the need for expert graders along with better technologies for remote imaging of the ocular fundus will allow for less expensive screening, which could enable screening of individuals with otherwise limited healthcare access. In India and China, where most glaucoma remains undiagnosed, glaucoma screening was recently found to be cost-effective. SUMMARY: Recent advances in artificial intelligence and telemedicine have the potential to increase the accuracy, reduce the costs, and extend the reach of screening. Further research into implementing these technologies in glaucoma screening is required.

Phacoemulsification vs phacoemulsification with micro-bypass stent implantation in primary angle closure and primary angle closure glaucoma: A randomized single-masked clinical study.

IMPORTANCE: Primary angle closure glaucoma (PACG) is a major cause of irreversible visual impairment in Asia, but there is no published data on the effect of iStent on these patients. BACKGROUND: To compare the efficacy and safety of combined phacoemulsification and iStent implantation with standard phacoemulsification in an Asian population. DESIGN: A prospective, single-masked, randomized study in a public tertiary eye clinic. PARTICIPANTS: Patients with concomitant visually significant cataracts and primary angle closure (PAC) or PACG. METHODS: Patients were randomized and underwent either phacoemulsification alone (phaco) or with concurrent iStent injection (phaco-iStent). Demographic and clinical data were collected. MAIN OUTCOME MEASURES: Complete and qualified success rates at 12 months were compared between both treatment arms. RESULTS: Thirty-two patients were recruited between September 2015 and February 2016. All patients completed 12 months of follow-up. There was no statistically significant difference in preoperative IOP (phaco, 17.5 ± 3.1 mmHg; phaco-iStent, 18.6 ± 4.7 mmHg, P = .65) and 12-months postoperative IOP (phaco, 15.0 ± 2.5 mmHg; phaco-iStent, 14.7 ± 3.1 mmHg, P = .86) between both groups. Complete success rates were 43.8% (95% CI, 19.8-65.6) for the Phaco group and 87.5% (95% CI, 58.6-96.7) for the Phaco-iStent group (P = .01). Thinner preoperative optical coherence tomography (retinal nerve fibre layer) thickness (hazard ratio [HR] = 7.34 [95% CI, 1.53-35.30]) and phacoemulsification alone (HR = 0.93 [95% CI, 0.87-0.02]) were independent factors associated with failure to achieve complete success. CONCLUSIONS AND RELEVANCE: Combined phacoemulsification with iStent implantation is associated with a higher likelihood of complete success compared with phacoemulsification alone in eyes with primary angle closure disease at 12 months postoperatively. Further studies are required to establish the longer term efficacy of iStent implantation and to identify other predictors for surgical success.

Myopic optic disc changes and its role in glaucoma.

PURPOSE OF REVIEW: Optic nerve head (ONH) changes such as tilt and torsion are associated with the progression of myopia, and may in turn predispose toward glaucoma. At the same time, these ONH deformations also make the structural assessment for glaucoma difficult. Here, we review the mechanisms and changes to the myopic optic disc, and the advances in structural imaging to better evaluate the ONH in myopia. RECENT FINDINGS: The distance, depth, and angle between the optic disc and the deepest point of the elongated eyeball may be related to the degree and direction of optic disc tilt and torsion. It is hypothesized that as the eyeball grows axially, the disc is pulled toward its most protruded point. These ONH deformations in myopia are thought to induce strain on the lamina cribrosa and the axons passing through it. Recent studies have shown unique characteristics of the lamina cribrosa in myopia that may account for susceptibility toward glaucoma. New developments in imaging the ONH in myopia, including the use of optical coherence tomography-angiography may also further our understanding of the relationship between myopia and glaucoma. SUMMARY: Optic disc changes in myopia are secondary to the configuration of the posterior globe. These ONH deformations may predispose toward glaucoma, although the causative relationship between myopia and glaucoma remains to be further clarified.

Descemet membrane endothelial keratoplasty and glaucoma.

PURPOSE OF REVIEW: The aim of this review is to describe the relationship between Descemet membrane endothelial keratoplasty (DMEK) and glaucoma. RECENT FINDINGS: Glaucoma after DMEK is a serious complication that may cause permanent visual loss, affect donor endothelial cells and graft survival. The mechanisms of raised intraocular pressure (IOP) after DMEK include reverse pupillary block in the early postoperative period, and steroid response in the late phase. The reduced risk of immunogenic graft rejection after DMEK necessitates a shorter duration of steroids, which may in turn reduce the risk of steroid response. On the other hand, eyes with preexisting glaucoma that undergo DMEK may have a poorer prognosis than those without glaucoma. SUMMARY: Early recognition and treatment of raised IOP is important after DMEK. Accurate IOP measurements after DMEK may be difficult to obtain because of the presence of an air bubble, corneal oedema, and corneal irregularities. A prophylactic peripheral iridectomy is recommended to prevent reverse pupillary block. Patients should posture face-up and be evaluated in the early postoperative period, as patients may be asymptomatic despite raised IOP. In order to reduce the risk of steroid response, weaker steroids may be prescribed after 1-3 months without adverse effects on DMEK outcomes.

Optical coherence tomography angiography: a review of current and future clinical applications.

Optical coherence tomography angiography is a non-invasive imaging technique that now allows for simultaneous in vivo imaging of the morphology as well as the vasculature in the eye. In this review, we provide an update on the existing clinical applications of optical coherence tomography angiography technology from the anterior to posterior segment of the eye. We also discuss the limitations of optical coherence tomography angiography technology, as well as the caveats to the interpretation of images. As current optical coherence tomography angiography systems are optimized for the retina, most studies have focused on interpreting images from conditions such as age related macular degeneration and retinal vascular diseases. However, the interpretation of these optical coherence tomography angiography images should be taken in consideration with other multi-modal imaging to overcome the limitations of each technique. In addition, there are a growing variety of clinical applications for optical coherence tomography angiography imaging in optic nerve head evaluation for glaucoma and optic neuropathies. Further developments in anterior optical coherence tomography angiography have now allowed for evaluation of anterior segment pathology such as glaucoma, ocular surface diseases, corneal vascularisation, and abnormal iris vasculature. Future developments in software could allow for improved segmentation and image resolution with automated measurements and analysis.

Central corneal thickness in glaucoma.

PURPOSE OF REVIEW: The purpose of this review is to summarize the role of central corneal thickness (CCT) in the clinical management of a glaucoma patient. RECENT FINDINGS: The prognostic value of CCT is well recognized in patients with ocular hypertension. However, its predictive value in other glaucoma suspects and patients with established glaucoma is less certain. Tonometry artefacts can result from variations in CCT. However, an adequately validated correction algorithm for Goldmann applanation tonometry measurements does not exist. Newer methods of tonometry are potentially less influenced by CCT but are limited in their clinical use. There may also be biological and genetic associations between corneal thickness and glaucoma. Demographics, environmental factors, glaucoma treatment and the measurement device used have a significant influence on CCT, and should be considered when interpreting the effect of cornea thickness in patients with glaucoma. New measurements of the biomechanical properties of the cornea are likely to be better approximations of the globe biomechanics than CCT, but these require further evaluation. SUMMARY: The clinical significance of CCT is well recognized in the context of glaucoma diagnosis and management, though the extent of its importance remains debatable. Corneal biomechanical properties may be more significantly associated with glaucoma than CCT.

Optical Coherence Tomography Angiography for Anterior Segment Vasculature Imaging.

PURPOSE: To evaluate the application of an optical coherence tomography angiography (OCTA) system adapted for the assessment of anterior segment vasculature. DESIGN: Cross-sectional, observational study. PARTICIPANTS: Consecutive subjects with normal eyes on slit-lamp clinical examination and patients with abnormal corneal neovascularization. METHODS: All scans were performed using a commercially available AngioVue OCTA system (Optovue, Inc., Fremont, CA) using an anterior segment lens adapter and the split-spectrum amplitude decorrelation angiography algorithm. Each subject underwent scans from 4 quadrants (superior, inferior, nasal, and temporal) in each eye by 2 trained, independent operators. MAIN OUTCOME MEASURES: Analysis of signal strength, image quality, and reproducibility of corneal vascular measurements was performed. RESULTS: In our study of 20 normal subjects (10 men, 10 women; mean age, 25.3±7.8 years), we found good repeatability (κ coefficient, 0.76) for image quality score and good interobserver agreement for vasculature measurements (intraclass coefficient, 0.94). After optimization of the angiography scan protocol, vascular measurements within the regions of interest were compared in the superior versus inferior quadrants (mean vascular loops, 3.34±1.16 vs. 3.12 ± 0.90 [P = 0.768]; segment-to-loop ratio, 4.18±0.71 vs. 4.32±0.87 [P = 0.129]; fractal dimension [Df] value, 1.78±0.06 vs. 1.78±0.06 [P = 0.94]; vascular loop area, 25.9±14.5 vs. 25.9±10.7 × 10(-3) mm(2) [P = 0.21]) and nasal versus temporal quadrant (mean vascular loops, 2.89±0.98 vs. 3.57±0.99 [P < 0.001]; segment-to-loop ratio, 3.94±0.69 vs. 4.55±0.78 [P = 0.897]; Df value, 1.78±0.06 vs. 1.77±0.06 [P = 0.14]; vascular loop area, 29.7±15.7 vs. 22.1±7.1 × 10(-3) mm(2) [P = 0.38]. We then used the established OCTA scanning protocol to visualize abnormal vasculature successfully in 5 patients with various corneal pathologic features, including graft-associated neovascularization, postherpetic keratitis scarring, lipid keratopathy, and limbal stem cell deficiency. CONCLUSIONS: This preliminary study describes a method for acquiring OCTA images of the cornea and limbal vasculature with substantial consistency. This technique may be useful for the objective evaluation of corneal neovascularization in the future.

Mechanism and management of angle closure in uveitis.

PURPOSE OF REVIEW: To summarize the multiple mechanisms responsible for angle closure in uveitis and to outline the management principles and treatment modalities. RECENT FINDINGS: Angle closure in uveitis is a heterogeneous disease with multiple mechanisms. Recent advances in anterior segment imaging have provided insights into the mechanisms of angle closure in uveitis. Uveitic eyes with angle closure from pupil block require surgical iridectomy with mobilization of the peripheral iris and viscogoniosynechiolysis of both posterior synechiae and peripheral anterior synechiae. Systemic conditions associated with uveitis can result in anterior displacement of the iris-lens diaphragm, and present as acute angle closure. Pupil block is not the predominant mechanism in these eyes, and management is primarily medical. Data are limited on the optimal treatment of angle closure in uveitis, and the role of glaucoma filtration surgery, cataract extraction, minimally invasive glaucoma surgery and newer modalities of cycloablation require evaluation. SUMMARY: The management of angle closure in uveitis should adhere to the principles of managing both uveitic glaucoma and angle closure. Identification of the mechanism of angle closure in uveitic eyes may enable treatment to be targeted at the responsible mechanism.

Pretreatment anterior segment imaging during acute primary angle closure: insights into angle closure mechanisms in the acute phase.

OBJECTIVE: To describe anterior segment optical coherence tomography (ASOCT) parameters during acute primary angle closure (APAC) before therapeutic interventions and comparative analyses of biometric parameters of APAC eyes with fellow eyes. DESIGN: Prospective, comparative case series. PARTICIPANTS: Thirty-one consecutive patients with APAC. METHODS: All patients underwent ASOCT imaging of both eyes during the attack, before therapeutic interventions were administered. Custom software was used to measure anterior chamber depth (ACD), anterior chamber area (ACA), anterior chamber volume (ACV), iris curvature (I-Curv), iris area (I-Area), lens vault (LV), and angle opening distance (AOD750), trabecular iris space area (TISA750), and iris thickness (IT750) at 750 µm from the scleral spur. Multivariate logistic regression modeling using forward selection was used to determine the most important biometric variables associated with APAC compared with the fellow eye during the attack. MAIN OUTCOME MEASURES: Anterior segment biometric parameters associated with APAC. RESULTS: The mean age of the patients was 60.9±7.5 years, and 11 patients (35.5%) were male. The mean intraocular pressure was 3.8±9.2 mmHg in the APAC eye and 4.2±4.3 mmHg in the fellow eye before treatment (P <0.001). After adjustment for pupil diameter, APAC eyes had smaller ACD, ACA, ACV, I-Curv (all P <0.001), AOD750 (P = 0.037), TISA750 (P = 0.043), I-Area (P = 0.027), and IT750 (P = 0.002) and larger LV (P = 0.041) than fellow eyes. An optimal model consisting of 3 variables (pupil diameter, ACD, and I-Curv) explained 36.7% of the variance in APAC occurrence, with ACD accounting for 18.1% and I-Curv accounting for 14.1% of this variance. CONCLUSIONS: Shallower ACD and smaller I-Curv were the 2 main anterior segment biometric parameters associated with APAC during the attack. These findings present new insights into the anterior segment biometric parameters of APAC and fellow eyes before therapeutic interventions. Anatomic changes in the anterior segment explained only about one third of the variance in APAC occurrence, and the role of nonanatomic factors require further investigation.

Comparative efficacy and tolerability of topical prostaglandin analogues for primary open-angle glaucoma and ocular hypertension.

OBJECTIVE: To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension. DATA SOURCES: A literature search was performed in PubMed (1965-June 2013) and the Cochrane Library (1980-June 2013) using the search terms ocular hypertension, open-angle glaucoma, prostaglandin analogues, bimatoprost, latanoprost, tafluprost, and travoprost. Additional studies were searched from the reference lists of identified publications. STUDY SELECTION AND DATA EXTRACTION: In all, 32 randomized controlled trials comparing between PGAs (bimatoprost 0.03%, latanoprost 0.005%, tafluprost 0.0015%, and travoprost 0.004%) or PGA with timolol were selected. DATA SYNTHESIS: A network meta-analysis was conducted. Using timolol as reference, the relative risks (RRs) of achieving treatment success, defined as the proportion of patients achieving at least 30% IOP reduction, with 95% CIs, were as follows: bimatoprost, 1.59 (1.28-1.98); latanoprost, 1.32 (1.00-1.74); travoprost, 1.33 (1.03-1.72); and tafluprost, 1.10 (0.85-1.42). The mean IOP reductions after 1 month were 1.98 (1.50-2.47), 1.01 (0.55-1.46), 1.08 (0.59-1.57), and 0.46 (-0.41 to 1.33) mm Hg, respectively, and the results were sustained at 3 months. Bimatoprost was associated with the highest risk of developing hyperemia, whereas latanoprost had the lowest risk, with RRs (95% CI) of 4.66 (3.49-6.23) and 2.30 (1.76-3.00), respectively. CONCLUSIONS: Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.

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.

Indications, outcomes, and risk factors for failure in tectonic keratoplasty.

PURPOSE: Outcomes of corneal transplantation for tectonic indications and risk factors for (tectonic and physiologic) graft failure. DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutive patients who underwent keratoplasty for tectonic indications at the Singapore National Eye Centre (SNEC) between January 1, 1991, and December 1, 2009. METHODS: Clinical data and donor and recipient characteristics were recorded and analyzed from subjects in the prospective Singapore Corneal Transplant Study. MAIN OUTCOME MEASURES: (1) Tectonic (anatomic) failure defined as recurrence of corneal melt threatening tectonic integrity and requiring additional corneal grafting within 3 months of the primary procedure. (2) Physiologic failure defined as irreversible change in graft clarity preventing recovery in useful vision in grafts initially clear 2 weeks postoperatively. RESULTS: The mean age of the study cohort (n = 362, 193 male and 169 female subjects) was 51.5 ± 20.2 years, with a mean follow-up of 25.8 ± 18.7 months. Patients underwent penetrating keratoplasty (PK) (n = 142, 39.2%), anterior lamellar keratoplasty (ALK) (n = 127, 35.1%), or a peripheral corneoscleral patch graft (n = 93, 25.7%) most commonly for inflammation (n = 68, 18.8%), trauma (n = 66, 18.2%), or infection (n = 66, 18.2%). Risk factors for tectonic failure (18/362 eyes, 5.0%) were severe lid disease (odds ratio [OR], 6.1; 95% confidence interval [CI], 1.7-22.1; P = 0.006), central ALK (OR, 7.5; 95% CI, 1.8-32.4; P = 0.007), and peripheral grafts (OR, 5.7; 95% CI, 1.1-28.3; P = 0.035). Among anatomically successful central grafts (n = 223), the mean physiological graft survival was 96 months (95% CI, 83-110); Kaplan-Meier probabilities for survival at 10 years were 66.8% for ALK and 44.2% for PK. Active corneal inflammation (hazard ratio [HR], 2.5; 95% CI, 1.4-4.4; P = 0.003) and larger donor and recipient graft sizes of ≥ 9 mm (HR, 17.9; 95% CI, 2.3-140.3; P = 0.006) were risk factors for physiologic graft failure in anatomically successful eyes with central tectonic grafts. CONCLUSIONS: Patients with lid disease, central ALK, and peripheral grafts were at higher risk of anatomic failure. For anatomically successful cases with central tectonic grafts, active corneal inflammation and donor size ≥ 9 mm were risk factors for physiologic failure. In these cases, our results suggest that ALK had better physiologic graft survival outcomes than PK.

Investigating the macular choriocapillaris in early primary open-angle glaucoma using swept-source optical coherence tomography angiography.

Introduction: There has been a growing interest in the role of vascular factors in glaucoma. Studies have looked at the characteristics of macular choriocapillaris in patients with glaucoma but with conflicting results. Our study aims to use swept-source optical coherence tomography angiography (SS-OCTA) to evaluate macular choriocapillaris metrics in normal participants and compare them with patients with early primary open-angle glaucoma (POAG) (mean deviation better than -6dB). Methods: In this prospective, observational, cross-sectional study, 104 normal controls (157 eyes) and 100 patients with POAG (144 eyes) underwent 3 mm × 3mm imaging of the macula using the Plex Elite 9000 (Zeiss Meditec, Dublin, CA, USA). Choriocapillaris OCTA images were extracted from the device's built-in review software and were subsequently evaluated for the density and size of choriocapillaris flow deficits. Results: After adjusting for confounding factors, the density of flow deficits was independently higher in those aged 53 years and above (P ≤ 0.024) whereas the average flow deficit size was significantly larger in those aged 69 years and above (95% CI = 12.39 to 72.91; P = 0.006) in both normal and POAG patients. There were no significant differences in the density of flow deficits (P = 0.453) and average flow deficit size (P = 0.637) between normal and POAG participants. Conclusion: Our study found that macular choriocapillaris microvasculature on SS-OCTA is unaltered by subjects with POAG. This suggests that OCTA macular choriocapillaris may not be potentially helpful in differentiating early glaucoma from healthy eyes.

Anterior Segment Optical Coherence Tomography Angiography Following Trabecular Bypass Minimally Invasive Glaucoma Surgery.

Objective: To assess anterior segment optical coherence tomography angiography (AS-OCTA) imaging of the episcleral vessels before and after trabecular bypass minimally invasive glaucoma surgery (MIGS). Design: A prospective, clinical, single-centre, single-arm pilot feasibility study conducted at National University Hospital, Singapore. Subjects: Patients with primary glaucomatous optic neuropathy undergoing Hydrus Microstent (Ivantis Inc., Irvine, CA, USA) implantation, who require at least one intra-ocular pressure-lowering medication. One or two eyes per patient may be enrolled. Methods: We performed AS-OCTA (Nidek RS-3000 Advance 2, Gamagori, Japan) pre- and up to 6 months post-MIGS implantation using a standard protocol in all cornealimbal quadrants, to derive episcleral vessel densities (VD) using a previously described technique. Main Outcome Measures: Episcleral VD pre- and post-surgery, in sectors with and without the implant. Results: We obtained serial AS-OCTA images in 25 eyes undergoing MIGS implantation (23 subjects, mean age 70.3 ± 1.5, 61% female) with mean preoperative intraocular pressure (IOP) of 15.5 mmHg ± 4.0. We observed reductions in postoperative episcleral VD compared to preoperative VD at month 1 (mean difference -3.2, p = 0.001), month 3 (mean difference -2.94, p = 0.004) and month 6 (mean difference -2.19, p = 0.039) in sectors with implants (overall 6 month follow-up, p = 0.011). No significant changes were detected in episcleral VD in the sectors without implants (p = 0.910). Conclusion: In our pilot study, AS-OCTA was able to detect changes in the episcleral VD following trabecular bypass MIGS, which may be a useful modality to evaluate surgical outcomes if validated in future studies.

Age-Related Eye Diseases in Individuals With Mild Cognitive Impairment and Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) and age-related eye diseases pose an increasing burden as the world's population ages. However, there is limited understanding on the association of AD/cognitive impairment, no dementia (CIND) with age-related eye diseases. Methods: In this cross-sectional, memory clinic-based study of multiethnic Asians aged 50 and above, participants were diagnosed as AD (n = 216), cognitive impairment, no dementia (CIND) (n = 252), and no cognitive impairment (NCI) (n = 124) according to internationally accepted criteria. Retinal photographs were graded for the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) using standard grading systems. Multivariable-adjusted logistic regression models were used to determine the associations between neurological diagnosis and odds of having eye diseases. Results: Over half of the adults had at least one eye disease, with AMD being the most common (60.1%; n = 356), followed by DR (8.4%; n = 50). After controlling for age, sex, race, educational level, and marital status, persons with AD were more likely to have moderate DR or worse (OR = 2.95, 95% CI = 1.15-7.60) compared with NCI. In the fully adjusted model, the neurological diagnosis was not associated with AMD (OR = 0.75, 95% CI = 0.45-1.24). Conclusion: Patients with AD have an increased odds of having moderate DR or worse, which suggests that these vulnerable individuals may benefit from specific social support and screening for eye diseases.

The development of a glaucoma-specific health-related quality of life item bank supporting a novel computerized adaptive testing system in Asia.

BACKGROUND: A glaucoma-specific health-related quality of life (HRQoL) item bank (IB) and computerized adaptive testing (CAT) system relevant to Asian populations is not currently available. We aimed to develop content for an IB focusing on HRQoL domains important to Asian people with glaucoma; and to compare the content coverage of our new instrument with established glaucoma-specific instruments. METHODS: In this qualitative study of glaucoma patients recruited from the Singapore National Eye Centre (November 2018-November 2019), items/domains were generated from: (1) glaucoma-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with glaucoma patients (n = 27); and (4) feedback from glaucoma experts. Data were analyzed using the constant comparative method. Items were systematically refined to a concise set, and pre-tested using cognitive interviews with 27 additional glaucoma patients. RESULTS: Of the 54 patients (mean ± standard deviation [SD] age 66.9 ± 9.8; 53.7% male), 67 (62.0%), 30 (27.8%), and 11 (10.2%) eyes had primary open angle glaucoma, angle closure glaucoma, and no glaucoma respectively. Eighteen (33.3%), 11 (20.4%), 8 (14.8%), 12 (22.2%), and 5 (9.3%) patients had no, mild, moderate, severe, or advanced/end-stage glaucoma (better eye), respectively. Initially, 311 items within nine HRQoL domains were identified: Visual Symptoms, Ocular Comfort Symptoms, Activity Limitation, Driving, Lighting, Mobility, Psychosocial, Glaucoma management, and Work; however, Driving and Visual Symptoms were subsequently removed during the refinement process. During cognitive interviews, 12, 23 and 10 items were added, dropped and modified, respectively. CONCLUSION: Following a rigorous process, we developed a 221-item, 7-domain Asian glaucoma-specific IB. Once operationalised using CAT, this new instrument will enable precise, rapid, and comprehensive assessment of the HRQoL impact of glaucoma and associated treatment efficacy.

Multivariate Normative Comparison, a Novel Method for Improved Use of Retinal Nerve Fiber Layer Thickness to Detect Early Glaucoma.

PURPOSE: Detection of early glaucoma remains limited with the conventional analysis of the retinal nerve fiber layer (RNFL). This study assessed whether compensating the RNFL thickness for multiple demographic and anatomic factors improves the detection of glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: Three hundred eighty-seven patients with glaucoma and 2699 healthy participants. METHODS: Two thousand six hundred ninety-nine healthy participants were enrolled to construct and test a multivariate compensation model, which then was applied in 387 healthy participants and 387 patients with glaucoma (early glaucoma, n = 219; moderate glaucoma, n = 97; and advanced glaucoma, n = 71). Participants underwent Cirrus spectral-domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. The RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. MAIN OUTCOME AND MEASURES: Measured and compensated RNFL thickness measurements. RESULTS: After applying the Asian-specific compensation model, the standard deviation of RNFL thickness reduced, where the effect was greatest for Chinese participants (16.9%), followed by Malay participants (13.9%), and Indian participants (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC, 0.90 vs. 0.85; P < 0.001), moderate glaucoma (AUC, 0.94 vs. 0.91; P < 0.001), and advanced glaucoma (AUC, 0.98 vs. 0.96; P < 0.001). CONCLUSIONS: The multivariate normative database of RNFL showed better glaucoma discrimination capability than conventional age-matched comparisons, suggesting that accounting for demographic and anatomic variance in RNFL thickness may have usefulness in improving glaucoma detection.

A multi-regression framework to improve diagnostic ability of optical coherence tomography retinal biomarkers to discriminate mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Diagnostic performance of optical coherence tomography (OCT) to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains limited. We assessed whether compensating the circumpapillary retinal nerve fiber layer (cpRNFL) thickness for multiple demographic and anatomical factors as well as the combination of macular layers improves the detection of MCI and AD. METHODS: This cross-sectional study of 62 AD (n = 92 eyes), 108 MCI (n = 158 eyes), and 55 cognitively normal control (n = 86 eyes) participants. Macular ganglion cell complex (mGCC) thickness was extracted. Circumpapillary retinal nerve fiber layer (cpRNFL) measurement was compensated for several ocular factors. Thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between the groups. The main outcome measure was OCT thickness measurements. RESULTS: Participants with MCI/AD showed significantly thinner measured and compensated cpRNFL, mGCC, and altered retinal vessel density (p < 0.05). Compensated RNFL outperformed measured RNFL for discrimination of MCI/AD (AUC = 0.74 vs 0.69; p = 0.026). Combining macular and compensated cpRNFL parameters provided the best detection of MCI/AD (AUC = 0.80 vs 0.69; p < 0.001). CONCLUSIONS AND RELEVANCE: Accounting for interindividual variations of ocular anatomical features in cpRNFL measurements and incorporating macular information may improve the identification of high-risk individuals with early cognitive impairment.