Sustainable practice of ophthalmology during COVID-19: challenges and solutions.

PURPOSE: The Coronavirus (COVID-19) outbreak is rapidly emerging as a global health threat. With no proven vaccination or treatment, infection control measures are paramount. In this article, we aim to describe the impact of COVID-19 on our practice and share our strategies and guidelines to maintain a sustainable ophthalmology practice. METHODS: Tan Tock Seng Hospital (TTSH) Eye Centre is the only ophthalmology department supporting the National Centre for Infectious Diseases (NCID), which is the national screening center and the main center for management of COVID-19 patients in Singapore. Our guidelines during this outbreak are discussed. RESULTS: Challenges in different care settings in our ophthalmology practice have been identified and analyzed with practical solutions and guidelines implemented in anticipation of these challenges. First, to minimize cross-infection of COVID-19, stringent infection control measures were set up. These include personal protective equipment (PPE) for healthcare workers and routine cleaning of "high-touch" surfaces. Second, for outpatient care, a stringent dual screening and triaging process were carried out to identify high-risk patients, with proper isolation for such patients. Administrative measures to lower patient attendance and reschedule appointments were carried out. Third, inpatient and outpatient care were separated to minimize interactions. Last but not least, logistics and manpower plans were drawn up in anticipation of resource demands and measures to improve the mental well-being of staff were implemented. CONCLUSION: We hope our measures during this COVID-19 pandemic can help ophthalmologists globally and serve to guide and maintain safe access in ophthalmology clinics when faced with similar disease outbreaks.

Optical coherence tomography angiography of the macula and optic nerve head: microvascular density and test-retest repeatability in normal subjects.

BACKGROUND: Despite the potential usefulness of optical coherence tomography angiography in retinal and optic disc conditions, the reliability of the imaging modality remains unclear. This study set out to measure the microvascular density of macula and optic disc by mean of optical coherence tomography angiography and report the repeatability of the vessel density measurements. METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability. RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%. CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system. TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Telemedicine screening for cytomegalovirus retinitis using digital fundus photography.

BACKGROUND: Screening for cytomegalovirus retinitis (CMVR) is important in patients with acquired immune deficiency syndrome and low CD4(+) counts. However, many human immunodeficiency virus (HIV) patients lack access to specialist ophthalmological care. Telemedicine screening is a cost-effective method for screening these patients. We aimed to report the use of composite nine-field digital fundus photography (DFP) images for CMVR screening. We report its sensitivity and specificity in detecting CMVR and the level of agreement with gold-standard binocular indirect ophthalmoscopy. MATERIALS AND METHODS: An audit was performed on our national CMVR screening program that screened all HIV patients referred to the Ophthalmology Department at Tan Tock Seng Hospital, Singapore. All patients underwent retinal screening with DFP. Images were categorized as CMVR-positive, CMVR-negative, suspicious, or unreadable by blinded retinal specialists. Patients subsequently underwent dilated gold-standard indirect ophthalmoscopy by a different retinal specialist. Diagnoses were categorized as CMVR-positive, CMVR-negative, or unreadable. Sensitivity and specificity of retinal findings on DFP and kappa values for level of agreement between the two screening methods were calculated. RESULTS: Three hundred seventy screenings on 188 patients were performed. Twenty-three eyes diagnosed with CMVR on indirect ophthalmoscopy were also identified on DFP (100% sensitivity). A 99.9% specificity was achieved. The fundus photograph of one eye without CMVR was read as CMVR-positive because of an artifact, accounting for a false-positive. Kappa values ranged from 0.739 to 0.987. CONCLUSIONS: DFP is a sensitive and specific method of screening HIV patients for CMVR and has a high level of agreement with indirect ophthalmoscopy.

Prospective 12-month outcomes of combined iStent inject implantation and phacoemulsification in Asian eyes with normal tension glaucoma.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Normal tension glaucoma (NTG) is a subset of open-angle glaucoma, demonstrating glaucomatous optic nerve damage in the absence of raised intraocular pressure (IOP). NTG is more prevalent in Asian populations. While generally slow-progressing, NTG may be associated with significant central visual field loss. In recent years, minimally invasive glaucoma surgery has been added to the armamentarium of glaucoma surgery. This prospective study aims to evaluate 12-month surgical outcomes of combined iStent inject (Glaukos Corporation, Laguna Hills, CA) implantation and phacoemulsification in Asian eyes with NTG. METHODS: This is a prospective, single-centre case series of 30 eyes followed up until 12 months after surgery. Outcome measures included IOP, number of glaucoma medications, best-corrected visual acuity (BCVA) and intra and postoperative complications. RESULTS: Mean age of subjects was 73.1 ± 6.3 years. Majority were ethnic Chinese (n = 27, 90%). Baseline medicated mean IOP was 13.8 ± 2.4 mmHg and mean number of glaucoma medications was 1.3 ± 0.7. Mean Humphrey visual field mean deviation was - 13.7 ± 7.6. The mean IOP reduction at all timepoints from postoperative month (POM) 3 onwards was statistically significant (all P < 0.05), with mean reduction of 1.2 mmHg (95% CI: 0.1-2.2, P = 0.037) by POM12. There was statistically significant reduction in mean number of medications from postoperative day (POD) 1 onwards (all P < 0.05), with mean decrease of 1.0 medication (95% CI: 0.9-1.1, P < 0.001) by POM12. By POM12, 25 (83.3%) eyes were medication-free. Three (10%) eyes had stent occlusion by iris requiring laser iridoplasty. One eye had gross hyphema which resolved on conservative management before POM1. Mean BCVA improved from the baseline 0.3 ± 0.3 logMAR to 0.1 ± 0.1 logMAR postoperatively (P < 0.001). There were no major adverse or sight-threatening events. No eyes required further glaucoma surgery during the 12-month follow-up period. CONCLUSION: Asian eyes with NTG which underwent combined iStent inject implantation and phacoemulsification demonstrated a significant and sustained reduction in IOP and glaucoma medications, up to 12 months postoperatively.

Comparison of the influence of cataract and pupil size on retinal nerve fibre layer thickness measurements with time-domain and spectral-domain optical coherence tomography.

BACKGROUND: To investigate and compare the effect of cataract and pupil size on retinal nerve fibre layer (RNFL) thickness measurements using spectral-domain optical coherence tomography (Cirrus OCT) and time-domain OCT (Stratus OCT). DESIGN: Prospective, hospital-based study. PARTICIPANTS: Twenty-five eyes from 25 normal subjects undergoing cataract surgery. METHODS: Three retinal nerve fibre layer (RNFL) thickness measurements were taken before and after dilation, preoperatively and postoperatively, using Cirrus 200×200 Optic Disc Scan and Stratus Fast RNFL Scan. MAIN OUTCOME MEASURES: Linear regression, intraclass correlation coefficient (ICC) and coefficient of variation analysis. RESULTS: Cataract removal caused significant increase in RNFL measurements in both modalities (Cirrus P<0.02; Stratus P<0.001). There was no significant difference in the increase in measurements between the two machines. Pupil dilation had variable and non-statistically significant effect in both (P>0.05). ICC showed excellent reproducibility with Cirrus OCT after mydriasis, preoperatively (ICC=0.78-0.90) and postoperatively (ICC=0.90-0.97), but poor reproducibility before mydriasis (P<0.75). Stratus OCT achieved excellent reproducibility after cataract removal both before (ICC=0.86-0.96) and after mydriasis (ICC=0.92-0.95), but poor reproducibility before cataract surgery (P<0.75). CONCLUSIONS: Cataracts, not pupil size, cause significant underestimation of RNFL measurements in both Cirrus and Stratus OCT. The extent of influence exerted does not appear different between the two instruments. Reproducibility of each machine appears to be affected differently. Mydriasis is required to achieve excellent reproducibility with Cirrus OCT, and media clarity is required with Stratus OCT.

Acute Onset of Bilateral Follicular Conjunctivitis in two Patients with Confirmed SARS-CoV-2 Infections.

PURPOSE: To report bilateral follicular conjunctivitis in two confirmed Coronavirus (COVID-19) patients with the presence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens. PARTICIPANTS AND METHODS: Two unrelated patients with confirmed SARS-CoV-2 infection and bilateral acute conjunctivitis were examined. Conjunctival swabs were assessed for the presence of SARS-CoV-2 by quantitative real-time polymerase chain reaction (RT-PCR) and viral culture. RESULTS: Both patients developed eye redness 3 days after the onset of COVID-19 symptoms. Slit lamp examination showed bilateral acute follicular conjunctivitis, which was resolved within 6 days. RT-PCR demonstrated the presence of viral RNA in conjunctival specimens from both eyes, which was unrelated to viral RNA from throat swabs. CONCLUSION: SARS-CoV-2 may cause ocular manifestations such as viral conjunctivitis. Conjunctival sampling may be useful for infected patients with conjunctivitis and fever. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection.

Evolving Practice Patterns in Singapore's Public Sector Ophthalmology Centers During the COVID-19 Pandemic.

Coronavirus disease 19 (COVID-19) was first reported in Wuhan, China, in December 2019, and has since become a global pandemic. Singapore was one of the first countries outside of China to be affected and reported its first case in January 2020. Strategies that were deployed successfully during the 2003 outbreak of severe acute respiratory syndrome have had to evolve to contain this novel coronavirus. Like the rest of the health care services in Singapore, the practice of ophthalmology has also had to adapt to this rapidly changing crisis. This article discusses the measures put in place by the 3 largest ophthalmology centers in Singapore's public sector in response to COVID-19, and the challenges of providing eye care in the face of stringent infection control directives, staff redeployments and "social distancing." The recently imposed "circuit breaker," effectively a partial lockdown of the country, has further limited our work to only the most essential of services. Our staff are also increasingly part of frontline efforts in the screening and care of patients with COVID-19. However, this crisis has also been an opportunity to push ahead with innovative practices and given momentum to the use of teleophthalmology and other digital technologies. Amidst this uncertainty, our centers are already planning for how ophthalmology in Singapore will be practiced in this next stage of the COVID-19 pandemic, and beyond.

Effects of primary glaucoma on sleep quality and daytime sleepiness of patients residing at an equatorial latitude.

AIM: To investigate the impact of primary glaucoma on sleep quality and daytime sleepiness of patients. METHODS: Prospective cross-sectional study with consecutive sampling in South-East Asian population was performed. Validated questionnaires: the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered prospectively. Subjects with non-glaucomatous optic neuropathy or concomitant retinal pathology were excluded. Glaucoma severity was based on HVF 24-2 perimetry. Binocular single vision was represented based on the better eye. Frequency of and predictive factors for poor sleep quality and excessive daytime sleepiness were compared. RESULTS: A total of 79 primary open angle glaucoma (POAG), 27 primary angle-closure glaucoma (PACG) patients, and 89 controls were recruited. PACG patients had higher median PSQI scores (P=0.004) and poorer sleep quality (P<0.001). Compared to controls, PACG patients were 3.34 times more likely to have poor sleep quality (P=0.008), which remained significant after adjustment for demographics (P=0.016) and predictive variables (P=0.013). PACG patients have poorer sleep quality when visual acuity (VA) was 6/15 or worse (P=0.009). Univariate and multivariate analysis of predictive variables for poor sleep quality and daytime sleepiness did not find statistical significance. CONCLUSION: PACG patients have poorer sleep quality but not daytime sleepiness. This is important in South-East Asian population with heavy disease burden. Evaluations on sleep disturbances can be considered to provide more holistic care.

Optical Coherence Tomography Angiography of Optic Disc and Macula Vessel Density in Glaucoma and Healthy Eyes.

AIM: To study the microvascular density of the macular and optic nerve head in healthy and glaucoma subjects using optical coherence tomography angiography. METHODOLOGY: We performed a cross-sectional cohort study on healthy subjects and patients with glaucoma. The AngioVue Enhanced Microvascular Imaging System was used to capture the optic nerve head and macula images during one visit. En face segment images of the macular and optic disc were studied in layers. Microvascular density of the optic nerve head and macula were quantified by the number of pixels measured by a novel in-house developed software. Areas under the receiver operating characteristic curves (AUROC) were used to determine the accuracy of differentiating between glaucoma and healthy subjects. RESULTS: A total of 24 (32 eyes) glaucoma subjects (57.5±9.5-y old) and 29 (58 eyes) age-matched controls (51.17±13.5-y old) were recruited. Optic disc and macula scans were performed showing a greater mean vessel density (VD) in healthy compared with glaucoma subjects. The control group had higher VD than the glaucoma group at the en face segmented layers of the optic disc (optic nerve head: 0.209±0.05 vs. 0.110±0.048, P<0.001; vitreoretinal interface: 0.086±0.045 vs. 0.052±0.034, P=0.001; radial peripapillary capillary: 0.146±0.040 vs. 0.053±0.036, P<0.001; and choroid: 0.228±0.074 vs. 0.165±0.062, P<0.001). Similarly, the VD at the macula was also greater in controls than glaucoma patients (superficial retina capillary plexus: 0.115±0.016 vs. 0.088±0.027, P<0.001; deep retina capillary plexus: 0.233±0.027 vs. 0.136±0.073, P<0.001; outer retinal capillary plexus: 0.190±0.057 vs. 0.136±0.105, P=0.036; and choriocapillaris: 0.225±0.053 vs. 0.153±0.068, P<0.001. The AUROC was highest for optic disc radial peripapillary capillary (0.96), followed by nerve head (0.92) and optic disc choroid (0.76). At the macula, the AUROC was highest for deep retina (0.86), followed by choroid (0.84), superficial retina (0.81), and outer retina (0.72). CONCLUSIONS: Microvascular density of the optic disc and macula in glaucoma patients was reduced compared with healthy controls. VD of both optic disc and macula had a high diagnostic ability in differentiating healthy and glaucoma eyes.

Trends in registered blindness and its causes over 19 years in Western Australia.

PURPOSE: To estimate the population-based incidence rates of blindness registration and their trends over time in Western Australia. METHODS: A retrospective review was performed on all cases of bilateral blindness registered with the Association for the Blind of Western Australia between 1984 and 2002. The causes and mean age at blindness registration were ascertained and incidence rates of blindness due to various causes were calculated. RESULTS: A total of 3852 blind certificates were examined. From 1984 to 1994, the annual incidence of registered bilateral blindness decreased significantly at an average rate of 9.4% per year (p < 0.0001), but then rose at a mean rate of 4.1% per year (p < 0.0001). ARMD blindness similarly fell by 8.9% per year (p < 0.0001), but then rose after 1994 by 4.5% per year (p < 0.0001). The incidence due to glaucoma decreased at an average rate of 10.3% per year (p < 0.0001) until 1994 and then rose at 7.4% per year at borderline significance (p = 0.025). CONCLUSIONS: There has been a nonlinear decrease in the incidence of registered blindness, in particular glaucoma-related blindness, in Western Australia. Rates of total registered blindness and that due to ARMD fell from 1984 to 1994, but have risen since.

Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

Agreement of angle closure assessments between gonioscopy, anterior segment optical coherence tomography and spectral domain optical coherence tomography.

AIM: To determine angle closure agreements between gonioscopy and anterior segment optical coherence tomography (AS-OCT), as well as gonioscopy and spectral domain OCT (SD-OCT). A secondary objective was to quantify inter-observer agreements of AS-OCT and SD-OCT assessments. METHODS: Seventeen consecutive subjects (33 eyes) were recruited from the study hospital's Glaucoma clinic. Gonioscopy was performed by a glaucomatologist masked to OCT results. OCT images were read independently by 2 other glaucomatologists masked to gonioscopy findings as well as each other's analyses of OCT images. RESULTS: Totally 84.8% and 45.5% of scleral spurs were visualized in AS-OCT and SD-OCT images respectively (P<0.01). The agreement for angle closure between AS-OCT and gonioscopy was fair at k=0.31 (95% confidence interval, CI: 0.03-0.59) and k=0.35 (95% CI: 0.07-0.63) for reader 1 and 2 respectively. The agreement for angle closure between SD-OCT and gonioscopy was fair at k=0.21 (95% CI: 0.07-0.49) and slight at k=0.17 (95% CI: 0.08-0.42) for reader 1 and 2 respectively. The inter-reader agreement for angle closure in AS-OCT images was moderate at 0.51 (95% CI: 0.13-0.88). The inter-reader agreement for angle closure in SD-OCT images was slight at 0.18 (95% CI: 0.08-0.45). CONCLUSION: Significant proportion of scleral spurs were not visualised with SD-OCT imaging resulting in weaker inter-reader agreements. Identifying other angle landmarks in SD-OCT images will allow more consistent angle closure assessments. Gonioscopy and OCT imaging do not always agree in angle closure assessments but have their own advantages, and should be used together and not exclusively.

A Cytomegalovirus Retinitis Screening Program: Evaluation of Enrollment Criteria for HIV Patients in Singapore.

PURPOSE: Identification of optimal enrollment criteria for a CMVR screening program suitable for a resource-limited environment. METHODS: A prospective audit was performed on newly diagnosed HIV patients referred for CMVR screening with any of the following four criteria: (1) visual symptoms, (2) low CD4(+) counts (<50 cells/µL), (3) AIDS-defining illnesses (ADI), and/or (4) opportunistic infections (OI). Odds ratios for each of the demographic factors and enrollment criteria were calculated. Sensitivities, specificities, and workload reduction for the various combinations were determined. RESULTS: A total of 348 screening visits for 176 HIV patients were performed. While individually only ADI was statistically significant for increased CMVR risk, the combination of CD4(+) counts <50 cells/µL with either ADI or visual symptoms or all 3 criteria were also statistically significant. Two enrollment criteria, ADI and ADI with CD4(+) <50 cells/µL, demonstrated good sensitivities, specificities, and workload reduction. CONCLUSION: We propose ADI and possibly CD4(+) counts <50 cells/µL as enrollment criteria for CMVR screening.

Bilateral endogenous endophthalmitis associated with methicillin sensitive Staphylococcus aureus (MSSA) related tenosynovitis: case report.

Endogenous endophthalmitis is a rare, devastating intraocular infection associated with poor outcome often from late diagnosis. We present a case report of acute onset bilateral endogenous endophthalmitis caused by Methicillin Sensitive Staphylococcus Aureus causing tenosynovitis of carpometacarpal joint in a 64 year old man with Type II Diabetes Mellitus. To the best of our knowledge, this is the first case report of endogenous endophthalmitis following tenosynovitis. This case also highlights the fact that prompt diagnosis and treatment is the key for good outcome.