Development and Validation of Performance-Based Assessment of Daily Living Tasks in Age-Related Macular Degeneration.

Purpose: To establish the reliability and validity of five performance-based activities of daily living task tests (ADLTT), to correlate structure to function, to evaluate the impact of visual impairment (VI) on age-related macular degeneration (AMD), and to develop new outcome measures. Methods: A multidisciplinary team developed five ADLTTs: (1) reading test (RT); (2) facial expression (FE) recognition; (3) item search (IS) task; (4) money counting (MC) task; and (5) making a drink (MD), tested with binocular and monocular vision. ADLTTs were tested for known-group (i.e., difference between AMD group and controls) and convergent (i.e., correlation to other measures of visual function), validity metrics, and test-retest reliability in 36 patients with VI (visual acuity (logMAR VA > 0.4) in at least one eye caused by AMD versus 36 healthy controls without VI. Results: Compared to controls, AMD patients had a slower reading speed (-77.41 words/min; P < 0.001); took longer to complete MC using monocular worse eye and binocular vision (15.13 seconds and 4.06 seconds longer compared to controls, respectively; P < 0.001); and MD using monocular worse eye vision (9.37 sec; P = 0.033), demonstrating known-group validity. Only RT and MC demonstrated convergent validity, showing correlations with VA, contrast sensitivity, and microperimetry testing. Moderate to good test-retest reliability was observed for MC and MD (interclass correlation coefficient = 0.55 and 0.77; P < 0.001) using monocular worse eye vision. Conclusions: Real-world ADL functioning associated with VI-related AMD can be assessed with our validated ADLTTs, particularly MC and MD. Translational Relevance: This study validates visual function outcome measures that are developed for use in future clinical practice and clinical trials.

Pathogenesis of Central Serous Chorioretinopathy and the Link Between Choroidal Hyperpermeability and Retinal Pigment Epithelium Pump Reversal.

PURPOSE: To describe 6 cases of acute central serous chorioretinopathy (CSCR) and the response to laser treatment, focusing on the underlying pathogenic mechanism. METHODS: Multimodal imaging from 6 eyes of 6 patients with acute and recurrent CSCR were reviewed, including fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) at baseline and after laser therapy. RESULTS: In 3 of the 6 cases with acute CSCR, the hyporeflective lucency sign was identified with cross-sectional and en face OCT and co-localized with an intense active inkblot retinal pigment epithelium (RPE) leak on FA. The development of this sign was suggestive of active leakage into the subretinal space displacing overlying subretinal hyperreflective material (SHRM) and suggestive of a reversal of RPE pump function. All 6 cases were treated with focal laser to directly target the intense leakage points with remarkable resolution of the fluid due to destruction of the RPE cells mediating reversal of pump function. CONCLUSIONS: Unlike chronic CSCR in which degenerative changes of the RPE lead to oozing of fluid into the subretinal space, in acute forms of CSCR including bullous CSCR, there are focal leaks of the RPE that actively drive fluid into the subretinal space suggestive of RPE pump reversal. We propose that pachychoroid disease causes increased hydrostatic pressure and increased resistance to the RPE pump, thereby triggering a reversal in pump function. Understanding this concept can have therapeutic implications.

A practical model for effective eye care delivery in Southeast Asian rural communities: A proposal built based on experts' recommendations.

PURPOSE: To evaluate rural community-based eye care models from the perspective of community ophthalmology experts and suggest sustainable technological solutions for enhancing rural eye care delivery. METHODS: A semi-structured descriptive survey, using close-ended and open-ended questions, was administered to the experts in community ophthalmology sourced through purposive sampling. The survey was self-administered and was facilitated through online platforms or in-person meetings. Uniform questions were presented to all participants, irrespective of their roles. RESULTS: Surveyed participants (n = 22 with 15 from India and 7 from Nepal) in high-volume tertiary eye hospitals faced challenges with resources and rural outreach. Participants had mixed satisfaction with pre-operative screening and theatre resources. Delayed presentations and inexperienced surgeons contributed to the surgery complications. Barriers to rural eye care included resource scarcity, funding disparities, and limited infrastructure. In rural/peri-urban areas 87% of participants agreed with providing primary eye care services, with more than 60% of the experts not in agreement with the makeshift center model of eye care delivery. Key components for an effective eye care model are sustainability, accessibility, affordability, and quality. These can be bolstered through a healthcare management platform and a human-chain supply distribution system. CONCLUSION: Tailored interventions are crucial for rural eye care, emphasizing the need for stronger human resources, optimized funding, and community awareness. Addressing challenges pertinent to delayed presentation and surgical training is vital to minimizing complications, especially with advanced cataracts. Enhancements in rural eye care demand a comprehensive approach prioritizing accessibility, affordability, and consistent quality.

Monocular and Binocular Visual Function Assessments and Activities of Daily Living Performance in Age-Related Macular Degeneration.

PURPOSE: To evaluate the relationship between specific monocular and binocular visual function (VF) assessments with binocularly performed activities of daily living task tests (ADLTTs) in patients with age-related macular degeneration (AMD) and healthy controls. DESIGN: Prospective case-control cohort study. SUBJECTS: Thirty-six AMD patients and 36 controls. METHOD: Visual field assessments included monocular and binocular best-corrected visual acuity (BCVA), contrast sensitivity (CS), and monocular microperimetry testing for mean macula sensitivity, mean retina sensitivity (MRS), fixation area, and fixation distance from fovea (FDF). Age-related macular degeneration lesion area and sensitivity were measured on OCT and microperimetry, respectively. Participants performed 4 validated ADLTTs with binocular BCVA: (1) reading; (2) item-search; (3) money-counting; and (4) multi-step drink-making tasks. MAIN OUTCOME MEASURES: Spearman correlations and multivariate regression analysis, adjusted for age, sex, and potential correlation between the 2 eyes, were used to assess the relationship between monocular and binocular VF assessments, and ADLTT performance in both groups. RESULTS: Age-related macular degeneration patients had poorer VF (BCVA, CS, mean macula sensitivity, and MRS) compared with healthy controls. Monocular BCVA in both better- and worse-vision eyes was moderately correlated with the binocular reading speed and money-counting tasks in participants with AMD. In AMD, monocular worse eye CS, MRS, AMD lesion area on OCT, and lesion sensitivity on microperimetry showed moderate correlations to various ADLTTs, such as reading, money-counting, and drink-making. Similar findings were found in our AMD cohort on multivariate regression analysis. Fewer significant correlations were observed for the better-vision eye, whereas no correlations were observed for healthy controls between VF parameters and ADLTTs. In contrast, significant associations were observed between binocular BCVA and CS with binocular ADLTTs (reading and item-search tasks) but not in AMD patients. CONCLUSION: Although monocular BCVA remains the most common measure of VF, CS and microperimetry testing also show significant correlations with ADLTTs performance in AMD patients, and should be considered as complimentary VF-outcome measures in both clinical and research settings. Unlike healthy subjects, AMD patients do not rely on binocular VF for ADLTT function, with the worse-vision eye impacting binocular ADLTT function more than the better-vision eye. Therefore, the worse-vision eye should not be neglected during the management of AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Colour vision restrictions for driving: an evidence-based perspective on regulations in ASEAN countries compared to other countries.

Colour vision deficiency is an impairment in discriminating colours. Beyond occupational opportunities, colour vision-based restrictions may limit driving, which is a daily task for many people. This review aims to compare existing colour vision requirements for obtaining a driving license in southeast Asian countries to the rest of the world. Subsequently, to review existing published literature and provide evidence-based recommendations for future guidelines for colour-deficient drivers. Color vision requirements for obtaining a driving license vary widely amongst countries. While colour-deficient drivers may face mild challenges in driving, increased awareness and developing effective compensatory strategies could enable them to drive safely. The current evidence does not support a strict exclusion of all colour-deficient individuals from driving. Instead, emphasis is needed on screening to increase awareness and insight into their disability. Future studies should consider compensatory adaptive strategies that are specific for high-risk situations such as challenging driving conditions.

Genetic Variability of Complement Factor H Has Ethnicity-Specific Associations With Choroidal Thickness.

Purpose: To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort. Methods: A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort. Results: A total of 1045 healthy Asian individuals (550 Chinese, 147 Indians, 348 Malays) were prospectively enrolled in the study. Several CFH alleles (rs800292, rs1061170, and rs1329428) were associated with increased SFCT in Indians (+18.7 to +31.7 µm; P = 0.001-0.038) and marginally associated with decreased SFCT in Malays (-12.7 to -20.6 µm; P = 0.014-0.022). Haplotype analysis of CFH revealed variable associations with SFCT among races, with the H6 haplotype being associated with a 29.08-µm reduction in SFCT in the Chinese cohort (P = 0.02) but a 35.2-µm increase in SFCT in the Indian cohort (P < 0.001). Finally, subfield analysis of the Chinese cohort identified associations between the CFH risk allele rs1061170 and reduced CT in the nasal and superior sectors (-20.2 to -25.8 µm; P = 0.003-0.027). Conclusions: CFH variants are variably associated with CT among Asian ethnic groups. This has broad implications for the pathogenesis of common diseases such as age-related macular degeneration and central serous choroidopathy, the pathogenesis of which is associated with CT.

Color vision restrictions for medical school admission: a discussion on regulations in ASEAN countries compared to countries across the world.

Color vision deficiency impairs one's ability to perceive and discriminate colors. Color-deficient individuals may face discrimination in various occupations, particularly in medical school admissions. This discussion seeks to compare the existing color vision requirements for entry to medical school in Southeast Asian countries as compared to countries across the world. Following this, we explore the published evidence in this field, to provide recommendations for future guidelines that will maximize the occupational opportunities for color-deficient individuals.

PATTERN AND CHARACTERISTICS OF DRUSEN SUBTYPES IN CHINESE AND INDIAN POPULATIONS IN SINGAPORE.

PURPOSE: To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness. METHODS: This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness. RESULTS: Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 µm; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 µm; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 µm; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 µm; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed. CONCLUSION: Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.

Initial experiences of switching to faricimab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in an Asian population.

Purpose: To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents. Methods: This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED. Results: Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (± SD)] VA, CST, and MV improved from 0.50 logMAR (± 0.27 logMAR) to 0.46 logMAR (± 0.27 logMAR) (p = 0.20), 383.35 µm (± 111.24 µm) to 322.46 µm (± 103.89 µm (p < 0.01), and 9.40 mm3 (± 1.52 mm3) to 8.75 mm3 (± 1.17 mm3) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 µm (± 151 µm) to 149 µm (± 113 µm) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 µm (± 217.97 µm)] and the post switch visit [236.66 µm (± 189.05 µm); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae. Conclusions: In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.

Serum Cholesterol Efflux Capacity in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Purpose: To investigate serum cholesterol efflux capacity (the ability of the serum to accept cholesterol) and factors that regulate it using nuclear magnetic resonance-quantified measures of lipoprotein particle composition and size and apolipoproteins metrics in patients with age-related macular degeneration (AMD). Design: Case-control study. Participants: Four hundred two serum samples from 80 patients with early AMD (eAMD), and 212 patients with neovascular AMD (nAMD), including 80 with typical nAMD (tAMD) and 132 with polypoidal choroidal vasculopathy (PCV), and 110 age- and gender matched control participants. Methods: Serum from participants showed cholesterol efflux capacity measured using in vitro cell assays and lipoprotein subfractions measured using nuclear magnetic resonance (Nightingale, Ltd). Associations between cholesterol efflux capacity (measured in percentage) and lipid subfractions were investigated in the patients and control participants. Main Outcome Measures: Cholesterol efflux capacity and lipid subfractions in control, eAMD, and nAMD. Associations between HDL subfractions and cholesterol efflux capacity. Results: Cholesterol efflux capacity was higher in patients with eAMD (68.0 ± 11.3% [mean ± standard deviation]) and nAMD (75.9 ± 27.7%) than in the control participants (56.9 ± 16.7%) after adjusting for age, gender, and use of lipid-lowering drug (P < 0.0001). Nuclear magnetic resonance lipidomics demonstrated that the mean diameter of HDL was larger both in eAMD (9.96 ± 0.27 mm [mean ± standard deviation]) and PCV (9.97 ± 0.23 mm) compared with that of the control participants (9.84 ± 0.24 mm; P = 0.0001 for both). Among the 28 HDL subfractions, most of the small, medium, and large HDLs, but none of the 7 extra large HDLs fractions, were associated moderately with cholesterol efflux capacity in eAMD and PCV (R = 0.149-0.277). Conclusions: Serum cholesterol efflux capacity was increased in eAMD and PCV, but not tAMD, possibly reflecting differential underlying pathophysiologic features of lipid dysregulation in tAMD and PCV. Further studies should be directed toward investigating the diverse biological activities of HDL in AMD, including macular pigment transport, regulation of inflammation, and local cholesterol transport system.

Efficacy of a novel personalised aflibercept monotherapy regimen based on polypoidal lesion closure in participants with polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy of aflibercept using a personalised versus fixed regimen in treatment-naïve participants with polypoidal choroidal vasculopathy (PCV). DESIGN: A 52-week, randomised, open-label, non-inferiority, single-centre study that included participants with symptomatic PCV. Participants were randomised (3:1 ratio) to receive either personalised (n=40) or fixed 8-weekly treatment regimen (n=13). The personalised regimen allowed for either early treat and extend (T&E) after week 12 or late T&E with 3 additional 4-weekly aflibercept injections until week 24 in participants with residual polypoidal lesions (PL) on indocyanine green angiography (ICGA) at week 12. MAIN OUTCOMES AND MEASURES: Non-inferiority of personalised to fixed regimen for mean change in best-corrected visual acuity (BCVA) from baseline to week 52 (non-inferiority margin: -5 letters). The key secondary outcomes include reduction in central subfield thickness (CSFT) on optical coherence tomography and the anatomical closure of PL on ICGA. RESULTS: Of the 53 participants, the mean (SD) age was 69.2 (8.1) years, 19 (35.8 %) were male. Personalised group was non-inferior to fixed for the primary end point (+8.1 vs +7.9 letters at week 52, respectively; difference 0.16, 95% CI -2.8 to 2.4, p=0.79). There was greater reduction in mean CSFT (SD) in the personalised versus fixed group (-248.8 (169.9) vs -164.8 (148.9) µm, p=0.03). Closure of PL occurred in 21 (55.2%) and 5 (41.6%) of study eyes in personalised and fixed groups, respectively at week 52 (p=0.41). CONCLUSIONS: Personalised regimen achieved non-inferior BCVA gain and numerically higher PL closure compared with fixed regimen. TRIAL REGISTRATION NUMBER: NCT03117634.

Impact of incident age-related macular degeneration and associated vision loss on vision-related quality of life.

BACKGROUND: We examined the associations between the 6-year incidence of age-related macular degeneration (AMD) and vision-related quality of life (VRQoL), and the contribution of presenting visual acuity (VA), in an Asian population. METHODS: Fundus images from the Singapore Chinese Eye Study, a population-based cohort study (baseline: 2009-2011; follow-up: 2015-2017), were graded using a modified Wisconsin age-related maculopathy grading system. Incident AMD was defined as no baseline AMD in both eyes and early/late AMD in the worse eye at follow-up. Presenting VA was assessed using the logarithm of the minimum angle of resolution chart at 4 m under standard lighting conditions with habitual correction. Multiple linear regression models determined the associations between AMD incidence with changes in the Rasch-transformed scores of the Reading, Mobility and Emotional VRQoL domains of the 32-item Impact of Visual Impairment (IVI-32) questionnaire, adjusted for traditional confounders. The contribution of presenting VA to changes in VRQoL was also estimated. RESULTS: Of the 2251 participants without AMD at baseline (mean age (SD): 57.7 (9) years, 51.4% women), 101 (4.5%) and 11 (0.5%) developed incident early and late AMD at follow-up, respectively. Incident late AMD was associated with significant 30.3%, 32.5% and 30.9% decrements in Reading, Mobility and Emotional IVI scores, respectively. The contribution of presenting VA ranged between 1.62% and 4.35% of the observed decrements. No significant associations were noted with incident early AMD. CONCLUSION: Incident late AMD had a substantial impact on all aspects of VRQoL, with presenting VA contributing only minimally to this longitudinal relationship.

OPTICAL COHERENCE TOMOGRAPHY FEATURES OF POLYPOIDAL LESION CLOSURE IN POLYPOIDAL CHOROIDAL VASCULOPATHY TREATED WITH AFLIBERCEPT.

PURPOSE: To evaluate whether optical coherence tomography (OCT) can determine polypoidal lesion (PL) perfusion in polypoidal choroidal vasculopathy eyes after 12 months of aflibercept monotherapy. Polypoidal lesion perfusion status, assessed by indocyanine green angiography, is an important anatomical outcome in polypoidal choroidal vasculopathy management. METHODS: Post hoc data from a prospective randomized, open-label, study in eyes with polypoidal choroidal vasculopathy undergoing monotherapy with aflibercept evaluated PL perfusion status based on indocyanine green angiography (gold standard) and OCT features from baseline to 12 months. RESULTS: Individual PLs (110 in total) from 48 eyes (48 patients) showed at 12 months; 57/110 PLs (51.8%) were closed on indocyanine green angiography. At 12 months, eyes with closed PLs were more likely to have the following OCT features: 1) no subretinal fluid (67.1% vs. 32.9%), 2) smaller pigment epithelial detachment height (67.2 [±43.8] vs. 189.2 [±104.9] µm), 3) densely hyperreflective pigment epithelial detachment contents (84.0% vs. 16.0%), 4) an absence of a hyperreflective ring(64.0% vs. 36.0%), and a 5) indistinct overlying retinal pigment epithelial (71.4% vs. 28.6%) (all P < 0.05). The three highest performing OCT features that differentiated perfused from closed PLs were (1), (3), and (4) (area under the receiver operating characteristic curve 0.85, 0.73, and 0.70, respectively). A combination of these three features achieved an area under the receiver operating characteristic curve of 0.90. CONCLUSION: Polypoidal lesion closure, an important anatomical treatment outcome in polypoidal choroidal vasculopathy typically defined by indocyanine green angiography, can be accurately detected by specific OCT features.

Identifying the content for an item bank and computerized adaptive testing system to measure the impact of age-related macular degeneration on health-related quality of life.

PURPOSE: We are developing an age-related macular degeneration (AMD) health-related quality of life (HRQoL) item bank, applicable to Western and Asian populations. We report primarily on content generation and refinement, but also compare the HRQoL issues reported in our study with Western studies and current AMD-HRQoL questionnaires. METHODS: In this cross-sectional, qualitative study of AMD patients attending the Singapore National Eye Centre (May-December 2019), items/domains were generated from: (1) AMD-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with AMD patients (n = 27); and (4) written feedback from retinal experts. Following thematic analysis, items were systematically refined to a minimally representative set and pre-tested using cognitive interviews with 16 AMD patients. RESULTS: Of the 27 patients (mean ± standard deviation age 67.9 ± 7.0; 59.2% male), 18 (66.7%), two (7.4%), and seven (25.9%) had no, early-intermediate, and late/advanced AMD (better eye), respectively. Whilst some HRQoL issues, e.g. activity limitation, mobility, lighting, and concerns were similarly reported by Western patients and covered by other questionnaires, others like anxiety about intravitreal injections, work tasks, and financial dependency were novel. Overall, 462 items within seven independent HRQoL domains were identified: Activity limitation, Lighting, Mobility, Emotional, Concerns, AMD management, and Work. Following item refinement, items were reduced to 219, with 31 items undergoing amendment. CONCLUSION: Our 7-domain, 219-item AMD-specific HRQoL instrument will undergo psychometric testing and calibration for computerized adaptive testing. The future instrument will enable users to precisely, rapidly, and comprehensively quantify the HRQoL impact of AMD and associated treatments, with item coverage relevant across several populations.

The Application of Optical Coherence Tomography Angiography in Systemic Hypertension: A Meta-Analysis.

Objective: Multiple studies have compared various optical coherence tomography angiography (OCTA) parameters in participants with systemic hypertension vs. controls and have presented discordant findings. We conducted a meta-analysis to pool together data from different studies to generate an overall effect size and find out whether OCTA parameter(s) significantly differed in participants with systemic hypertension as compared to controls. Methods: We conducted a literature search through a search of electronic databases to identify studies before 19 June 2021, which compared OCTA parameters in non-diabetic participants with systemic hypertension vs. controls. If the OCTA parameter had a minimum number of 3 studies that analyzed it, the mean difference between participants with systemic hypertension and controls were analyzed using a random-effects model. Results: We identified 11 eligible studies. At the macula, 9 studies analyzed vessel density at the superficial capillary plexus (SVD), 7 analyzed vessel density at the deep capillary plexus (DVD), and 6 analyzed the area of the superficial foveal avascular zone (FAZ). Participants with systemic hypertension had significantly lower SVD (standardized mean difference [SMD], -0.50 [-0.70, -0.30], P < 0.00001, I 2 = 63%), lower DVD (SMD, -0.38 [-0.64, -0.13], P = 0.004, I 2 = 67%) and larger superficial FAZ (SMD, 0.32 [0.04, 0.61], P = 0.020, I 2 = 77%). Conclusion: The eyes of people with systemic hypertension have robustly lower superficial and deep vascular densities at the macula when compared to control eyes. Our results suggest that OCTA can provide information about pre-clinical microvascular changes from systemic hypertension.

Developing a normative database for retinal perfusion using optical coherence tomography angiography.

Visualizing and characterizing microvascular abnormalities with optical coherence tomography angiography (OCTA) has deepened our understanding of ocular diseases, such as glaucoma, diabetic retinopathy, and age-related macular degeneration. Two types of microvascular defects can be detected by OCTA: focal decrease because of localized absence and collapse of retinal capillaries, which is referred to as the non-perfusion area in OCTA, and diffuse perfusion decrease usually detected by comparing with healthy case-control groups. Wider OCTA allows for insights into peripheral retinal vascularity, but the heterogeneous perfusion distribution from the macula, parapapillary area to periphery hurdles the quantitative assessment. A normative database for OCTA could estimate how much individual's data deviate from the normal range, and where the deviations locate. Here, we acquired OCTA images using a swept-source OCT system and a 12×12 mm protocol in healthy subjects. We automatically segmented the large blood vessels with U-Net, corrected for anatomical factors such as the relative position of fovea and disc, and segmented the capillaries by a moving window scheme. A total of 195 eyes were included and divided into 4 age groups: < 30 (n=24) years old, 30-49 (n=28) years old, 50-69 (n=109) years old and >69 (n=34) years old. This provides an age-dependent normative database for characterizing retinal perfusion abnormalities in 12×12 mm OCTA images. The usefulness of the normative database was tested on two pathological groups: one with diabetic retinopathy; the other with glaucoma.

Choriocapillaris microvasculature dysfunction in systemic hypertension.

We examined the choriocapillaris microvasculature using a non-invasive swept-source optical coherence tomography angiography (SS-OCTA) in 41 healthy controls and 71 hypertensive patients and determined possible correlations with BP and renal parameters. BP levels, serum creatinine and urine microalbumin/creatinine ratio (MCR) specimens were collected. The estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. The main outcome was choriocapillaris flow deficits (CFD) metrics (density, size and numbers). The CFD occupied a larger area and were fewer in number in the hypertensive patients with poor BP control (407 ± 10 µm2; 3260 ± 61) compared to the hypertensives with good BP control (369 ± 5 µm2; 3551 ± 41) and healthy controls (365 ± 11 µm2; 3581 ± 84). Higher systolic BP (ß = 9.90, 95% CI, 2.86-16.93), lower eGFR (ß = - 0.85; 95% CI, - 1.58 to - 0.13) and higher urine MCR (ß = 1.53, 95% CI, 0.32-2.78) were associated with larger areas of CFD. Similar significant associations with systolic BP, eGFR and urine MCR were found with number of CFD. These findings highlight the potential role of choriocapillaris imaging using SS-OCTA as an indicator of systemic microvascular abnormalities secondary to hypertensive disease.

Patterns and Determinants of Choroidal Thickness in a Multiethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To describe the distribution and determinants of choroidal thickness (CT) in participants in a population study based on spectral-domain (SD)-OCT measurements. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Ethnic Chinese, Indian, and Malay adults aged more than 50 years without any retinal diseases (e.g., diabetic retinopathy, macular edema, age-related macular degeneration, central serous chorioretinopathy) that might affect the CT were recruited from the Singapore Epidemiology of Eye Diseases Study. METHODS: Choroidal imaging was performed by SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany) in enhanced depth imaging (EDI) mode. Subfoveal choroidal thickness (SFCT) was measured on the foveal line scan by 2 retinal experts independently (YS and KT), and the average was used in the analyses. In Chinese and Indian cohorts in whom macular raster scans were captured, the manufacturer-supplied research software (Heyex SP-X version 6.4.8.116; Heidelberg Engineering) was used to obtain automated segmentation yielding mean choroidal thickness in each of the 9 ETDRS grid sectors. MAIN OUTCOME MEASURES: Subfoveal choroidal thickness and regional CT in the 9 ETDRS grid sectors. RESULTS: For the SFCT analysis, 2794 eyes of 1619 participants (Chinese, Indian, and Malay ) were included. The mean age was 60.9 years (standard deviation, 7.7), and 797 (49.2%) were male. Mean SFCT was 255.2 µm (standard deviation, 102.6). The normal range of SFCT was 106 to 447 µm (corresponding to 5th and 95th percentile limits of SFCT, respectively). In multivariable models, thinner SFCT was associated with older age, female gender, longer axial length, and Malay (vs. Chinese) ethnicity. In the subset of Chinese and Indian eyes (n = 1842) in whom regional variation was evaluated, the choroid was thickest at the superior and temporal sectors and thinner at the inferior and nasal sectors. CONCLUSIONS: Subfoveal choroidal thickness is influenced by age, gender, and ethnicity along with regional differences even within individual eyes. Subfoveal choroidal thickness also shows a wide range in physiologic limits. These data may be used as a reference in future studies.

Systemic hypertension associated retinal microvascular changes can be detected with optical coherence tomography angiography.

A major complication of hypertension is microvascular damage and capillary rarefaction is a known complication of hypertensive end-organ damage which confers a higher risk of systemic disease such as stroke and cardiovascular events. Our aim was to study the effect of hypertension on the retinal microvasculature using non-invasive optical coherence tomography angiography (OCTA). We performed a case-control study of 94 eyes of 94 participants with systemic hypertension and 46 normal control eyes from the Singapore Chinese Eye Study using a standardized protocol to collect data on past medical history of hypertension, including the number and type of hypertensive medications and assessed mean arterial pressure. Retinal vascular parameters were measured in all eyes using OCTA. In the multivariate analysis adjusting for confounders, compared to controls, eyes of hypertensive patients showed a decrease in the macular vessel density at the level of the superficial [OR 0.02; 95% CI, 0 to 0.64; P 0.027] and deep venous plexuses [OR 0.03; 95% CI, 0 to 0.41; P 0.009] and an increase in the deep foveal avascular zone. This shows that hypertension is associated with reduced retinal vessel density and an increased foveal avascular zone, especially in the deep venous plexus, as seen on OCTA and there is a potential role in using OCTA as a clinical tool to monitor hypertensive damage and identifying at risk patients.

Optical coherence tomography characteristics of taxane-induced macular edema and other multimodal imaging findings.

PURPOSE: To identify common optical coherence tomography (OCT) characteristics of taxane-related CME (T-CME) to differentiate it from CME associated with other causes (O-CME) and to present multimodal imaging findings of T-CME. METHODS: To differentiate T-CME from O-CME, pooled SD-OCT images from 14 previous publications and images obtained from our multicenter case series of 3 patients with multimodal imaging of T-CME were compared with 16 consecutive cases of O-CME. Images were graded by 2 masked retinal specialists based on the presence of pre-specified OCT characteristics such as CME centered around fovea, outer retinal cysts more prominent compared with inner retinal cysts, continuous outer plexiform layer (OPL) and inner plexiform layer (IPL), intact outer retina layer, attenuation of outer retina layers by overlying retinal layers, and the presence of subretinal fluid. RESULTS: Comparing 19 and 16 SD-OCT images of T-CME and O-CME, respectively, T-CME showed a significantly higher rate of the continuous OPL and IPL layer and a higher composite score of the various pre-specified OCT features. All other individual features showed no significant difference between T-CME and O-CME. All our patients had T-CME that had vague petalloid patterns on the late-stage FFA, with late leakage on ICGA. OCT angiography in one case showed an intact foveal avascular zone. CONCLUSIONS: T-CME is a rare but important complication of taxane chemotherapy. Specific OCT features such as an intact continuous OPL and IPL layer combined with other OCT features can help distinguish T-CME from O-CME, and early diagnosis is clinically important as cessation of taxanes before the retinal layers are disrupted may prevent permanent vision loss.