Publications by authors named "Edmund Wong"

61 Publications

Association of macular and choroidal perfusion with long-term visual outcomes after macula-off rhegmatogenous retinal detachment.

Br J Ophthalmol 2021 Apr 7. Epub 2021 Apr 7.

Ophthalmology and Visual Sciences Academic Clinical Program, Duke-National University of Singapore Medical School, Singapore

Background/aims: To examine the relationship between macular perfusion, as assessed using optical coherence tomography angiography (OCTA), and long-term visual outcome after surgical repair of macula-off rhegmatogenous retinal detachment (RRD).

Methods: A prospective study of 29 patients who had undergone successful surgical repair of macula-off RRD. OCTA imaging was performed at month 3 and repeated at months 6 and 12 after surgery. Associations between OCTA parameters including, foveal avascular zone (FAZ) area, vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris flow deficit features and logMAR best-corrected visual acuity (VA) were assessed using a random intercept hybrid linear mixed model.

Results: Over the 1-year follow-up, VA improved (0.025 logMAR/ month, 95% CI 0.015 to 0.035) and FAZ area decreased (-0.020 mm/month, 95% CI -0.032 to -0.007). Better VA after surgery was significantly associated with denser superficial VD (β=0.079, 95% CI 0.026 to 0.131), lower number of choriocapillaris flow deficits (β=-0.087, 95% CI -0.154 to -0.021) and larger average size of choriocapillaris flow deficits (β=0.085, 95% CI 0.022 to 0.147), after adjusting for baseline VA, types of surgery and other factors.

Conclusions: OCTA measures of vascular perfusion in the macula may provide new pathophysiological insights and prognostic information related to macula-off RRD.
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http://dx.doi.org/10.1136/bjophthalmol-2021-318907DOI Listing
April 2021

Retinal microvascular signs in COVID-19.

Br J Ophthalmol 2021 Mar 19. Epub 2021 Mar 19.

Singapore National Eye Centre, Singapore.

Background/aims: To explore if retinal findings are associated with COVID-19 infection.

Methods: In this prospective cross-sectional study, we recruited participants positive for COVID-19 by nasopharyngeal swab, with no medical history. Subjects underwent retinal imaging with an automated imaging device (3D OCT-1 Maestro, Topcon, Tokyo, Japan) to obtain colour fundus photographs (CFP) and optical coherence tomographic (OCT) scans of the macula. Data on personal biodata, medical history and vital signs were collected from electronic medical records.

Results: 108 patients were recruited. Mean age was 36.0±5.4 years. 41 (38.0%) had symptoms of acute respiratory infection (ARI) at presentation. Of 216 eyes, 25 (11.6%) had retinal signs-eight (3.7%) with microhaemorrhages, six (2.8%) with retinal vascular tortuosity and two (0.93%) with cotton wool spots (CWS). 11 eyes (5.1%) had hyper-reflective plaques in the ganglion cell-inner plexiform layer layer on OCT, of which two also had retinal signs visible on CFP (CWS and microhaemorrhage, respectively). There was no significant difference in the prevalence of retinal signs in symptomatic versus asymptomatic patients (12 (15.0%) vs 13 (9.6%), p=0.227). Patients with retinal signs were significantly more likely to have transiently elevated blood pressure than those without (p=0.03).

Conclusion: One in nine had retinal microvascular signs on ocular imaging. These signs were observed even in asymptomatic patients with normal vital signs. These retinal microvascular signs may be related to underlying cardiovascular and thrombotic alternations associated with COVID-19 infection.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985973PMC
March 2021

Liposomal drug delivery system for anti-inflammatory treatment after cataract surgery: a phase I/II clinical trial.

Drug Deliv Transl Res 2021 Feb 10. Epub 2021 Feb 10.

Singapore National Eye Centre (SNEC), 11 Third Hospital Avenue, Singapore City, 168751, Singapore.

Liposomes as a drug delivery system may overcome the problems associated with non-compliance to eyedrops and inadequate control of inflammation after cataract surgery. We evaluated the safety and efficacy of a single subconjunctival injection of liposomal prednisolone phosphate (LPP) for the treatment of post-cataract surgery inflammation. This is a phase I/II, open-label non-comparative interventional trial of patients undergoing cataract surgery. All patients received a single injection of subconjunctival LPP intraoperatively. The primary outcome measure was the proportion of eyes with an anterior chamber cell count of 0 at postoperative month 1. Ocular and non-ocular adverse events, including elevated intraocular pressure, rebound iritis and pseudophakic macular edema were monitored. Five patients were enrolled in this study. The mean age was 66.6 ± 6.2 and 4 (80%) were male. The proportion of patients with AC cell grading of 0 was 0%, 80%, 80%, and 100% at day 1, week 1, month 1, and month 2 after cataract surgery, respectively. Mean laser flare photometry readings were significantly elevated at week 1 after cataract surgery (48.8 ± 18.9, p = 0.03) compared with baseline, decreasing to 25.8 ± 9.2 (p = 0.04) at month 1 and returned to baseline by month 2 (10.9 ± 5.1, p = 1.0). No ocular or non-ocular adverse events were observed. Liposomal prednisolone phosphate, administered as a single subconjunctival injection intraoperatively, can be a safe and effective treatment for post-cataract surgery inflammation. The delivery of steroids with a liposomal drug delivery system could potentially replace eyedrops as anti-inflammatory therapy following cataract surgery.
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http://dx.doi.org/10.1007/s13346-021-00912-xDOI Listing
February 2021

Intravitreal Injection with a Conjunctival Injection Device: A Single-Center Experience.

Transl Vis Sci Technol 2020 07 17;9(8):28. Epub 2020 Jul 17.

Singapore National Eye Centre, Singapore.

Purpose: To evaluate the clinical performance of the intravitreal injection assistant device (InVitria) compared with the conventional freehand technique for delivering intravitreal injections.

Methods: Seventy patients were randomized to receive intravitreal injections via the conventional freehand technique while 70 received injections using the InVitria. Half of all procedures in each group were performed by junior surgeons, while the rest were performed by senior surgeons.

Results: Mean injections times were 90.0 ± 23.3 seconds and 64.9 ± 26.8 seconds for conventional versus InVitria ( < 0.001). Mean injection times with the conventional technique were 85.5 ± 23.0 seconds vs. 94.2 ± 23.0 seconds for senior versus junior surgeons ( = 0.120). Mean injection times with the InVitria were 56.1 ± 26.1 seconds vs. 66.3 ± 26.9 seconds ( = 0.211) for senior versus junior surgeons. There were no significant differences in pain scores regardless of technique (conventional versus In Vitria: 2.03 ± 1.73 vs. 2.13 ± 2.20, = 0.770).

Conclusions: In our experience, the InVitria is a comparable alternative to the conventional freehand technique of delivering intravitreal injections, with the potential for faster injection times and without compromising on patient comfort.

Translational Relevance: The study provides evidence to suggest that the InVitria may be deployed effectively in clinical practice.
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http://dx.doi.org/10.1167/tvst.9.8.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422773PMC
July 2020

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

Asia Pac J Ophthalmol (Phila) 2020 Jul-Aug;9(4):285-290

National Healthcare Group Eye Institute, Tan Tock Seng Hospital, National Healthcare Group, Singapore.

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.
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http://dx.doi.org/10.1097/APO.0000000000000306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402564PMC
August 2020

"Pauci-Hemosiderotic" Fibrolipomatous Tumor: A Mimicker of Various Lipomatous Lesions.

Int J Surg Pathol 2021 Feb 3;29(1):64-68. Epub 2020 Jun 3.

Queen Elizabeth Hospital, Kowloon, Hong Kong SAR, China.

Hemosiderotic fibrolipomatous tumor is a rare soft tissue tumor that preferentially affects the dorsum of foot, shows recurrent t(1;10) translocation targeting and () genes, and has a high recurrence potential. Hemosiderin deposits, mature adipocytes, and interspersed spindle cells are the 3 cardinal morphologic features of this tumor. We describe a "pauci-hemosiderotic" example involving the left wrist of a 45-year-old female, posing a diagnostic pitfall. The tumor comprised mature adipose tissue traversed by variably thick fibrous septa containing short fascicles of spindle cells. Prominent small- to medium-sized blood vessels were present, often with perivascular fibrosis or aggregates of foamy histiocytes, sometimes associated with red cell extravasation. Hemosiderin was not conspicuous, but fine deposits could be found focally on careful search and with the aid of Perls stain. The diagnosis was further confirmed by diffuse expression of CD34 and presence of translocation by fluorescence in situ hybridization. Pathologists should be aware that hemosiderin deposition can be scanty and focal in hemosiderotic fibrolipomatous, but the rich vasculature with a "damaged" appearance is a useful diagnostic clue.
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http://dx.doi.org/10.1177/1066896920930799DOI Listing
February 2021

25-years Trends and Risk factors related to Surgical Outcomes of Giant Retinal Tear-Rhegmatogenous Retinal Detachments.

Sci Rep 2020 03 25;10(1):5474. Epub 2020 Mar 25.

Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore.

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients' demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups - Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5 year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991-2005 and 2006-2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.
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http://dx.doi.org/10.1038/s41598-020-61592-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096512PMC
March 2020

Real-World Treatment Outcomes of Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Asians.

Ophthalmol Retina 2020 04 9;4(4):403-414. Epub 2019 Nov 9.

Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Republic of Singapore; Duke-NUS Graduate Medical School, Eye Academic Clinical Program, Singapore, Republic of Singapore. Electronic address:

Purpose: To describe the 12-month outcomes of treatment-naïve eyes with choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) after initiation of intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy or combination therapy with verteporfin photodynamic therapy (PDT).

Design: A 12-month single-center, retrospective, comparative, nonrandomized cohort study.

Participants: Patients with AMD or PCV who initiated intravitreal anti-VEGF therapy during 2015.

Methods: Demographics, visual outcomes, OCT, and treatment data were collected at baseline and months 1, 3, 6, and 12 after treatment initiation. Multivariate analysis was performed to identify baseline features predictive of visual maintenance and improvement after 12 months of treatment.

Main Outcome Measures: Primary end point was visual acuity (VA) change from baseline to month 12. Secondary end points were treatment exposure and change in central subfield thickness on OCT.

Results: A total of 364 patients (165 AMD and 199 PCV) were included. Baseline vision was 41 and 43 logarithm of the minimum angle of resolution (logMAR) letters for AMD and PCV patients, respectively. Patients with AMD and PCV received 5.5 and 5.3 injections (5.0 monotherapy vs. 5.6 combination therapy; mean, 1.2 PDT sessions), respectively. Patients with AMD gained 4.7 logMAR letters after 12 months (P = 0.002), whereas PCV patients gained 6.6 logMAR letters (P = 0.001) and 10.8 logMAR letters (P < 0.001) for monotherapy and combination therapy, respectively. Only patients with presenting VA of fewer than 35 letters (Snellen equivalent, 6/60) achieved significant visual improvement (10.4 letters for AMD, 17.1 letters for PCV with monotherapy, and 35.5 letters for PCV with combination therapy). Predictors of VA gain included number of intravitreal injections (AMD and PCV adjusted odds ratio, 12.1 [P = 0.001] and 12.5 [P = 0.004] for ≥7 injections, respectively) and baseline VA of 20 logMAR letters or fewer (adjusted odds ratio, 3.8 and 10.6 for AMD and PCV, respectively). Age, gender, race, use of PDT or focal laser therapy, and central subfield thickness were not predictive of significant visual gain at 12 months.

Conclusions: In Asian patients, treatment of AMD with anti-VEGF therapy yielded 12-month visual outcomes comparable with those of other real-world studies from Western populations but poorer than those of controlled trials. In contrast, for PCV eyes, anti-VEGF monotherapy and combination therapy with PDT yielded comparable outcomes as those of controlled clinical trials.
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http://dx.doi.org/10.1016/j.oret.2019.10.019DOI Listing
April 2020

Shared Care for Patients with Diabetes at Risk of Retinopathy: A Feasibility Trial.

Int J Integr Care 2019 Sep 18;19(3):18. Epub 2019 Sep 18.

Singapore National Eye Centre, SG.

Purpose: While diabetes is a chronic disease, in many health care systems patients with diabetes at risk of diabetic retinopathy (DR) are managed in hospital settings. Aim of this feasibility study is to assess the quality of care and economic benefits of a shared care model managing patients at risk of DR in a primary eye care clinic (PEC) compared with a current tertiary specialist outpatient clinic (SOC).

Methods: A randomized trial was performed, to compare a PEC with a SOC in Singapore. The trial patients included those previously seen at the SOC, and having no DR or stable mild non proliferative (NPDR) with no macular edema, no visual and DR deterioration. Primary outcomes were clinical management. Secondary outcomes were patient satisfaction and cost of consultation. Differences analysis used equivalence testing and generalized odds ratios (GOR).

Results: The trial included 231 patients, 83.1% classified as no DR (PEC: 79.1%; SOC: 87.1%) and 16.9% as stable mild NPDR (PEC: 20.9%; SOC: 12.9%). DR management at PEC was significantly equivalent to that received at the SOC (rate difference 2.56%; CI: (-1.61% to 6.74%)) and 4.29%; CI: (0.14%-8.45%), respectively. Patient satisfaction at the PEC was equally high when compared to SOC (GOR: 1.71; CI: (0.50-2.00)). Direct costs per patient visit was 45% lower at PEC compared to SOC.

Conclusions: Our feasibility trial showed that patients with diabetes with no or stable DR receive similar clinical care and management at a lower-cost PEC setting, are equally satisfied with the service compared to tertiary eye care. A follow-up study is necessary to validate these findings. Managing patients with diabetes at risk of DR at a PEC may be a safe and effective shared care model to improve accessibility for patients while enhancing professional collaboration between hospital and community settings.
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http://dx.doi.org/10.5334/ijic.4208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753306PMC
September 2019

Ipsilateral vocal fold paralysis: An unusual complication of internal jugular tunnelled dialysis catheter insertion.

J Vasc Access 2020 Jan 24;21(1):116-119. Epub 2019 Jun 24.

Department of Renal Medicine, Changi General Hospital, Singapore.

Background: Central venous catheters are extensively used in critical care units and in dialysis centres to gain access to the blood stream for the purpose of invasive monitoring, drug administration, parenteral nutrition and to perform renal replacement therapy. One of the common areas of central venous catheter insertion is right internal jugular vein due to its anatomical continuity with the superior vena cava. The complication rates of central venous catheter insertion can be more than 15%, including early and late complications.

Case Report: We present an unusual complication of recurrent laryngeal nerve palsy, leading to right vocal fold paralysis, following insertion of a right internal jugular tunnelled dialysis catheter. The vocal fold paralysis improved over next 8 months with conservative management alone.

Conclusion: This case illustrates an unusual complication of central venous catheter insertion and the importance of recognizing the possibility of such complications, to prevent them from happening and also to manage them appropriately.
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http://dx.doi.org/10.1177/1129729819856967DOI Listing
January 2020

Scaling of the corpus callosum in wild and domestic canids: Insights into the domesticated brain.

J Comp Neurol 2018 10 25;526(15):2341-2359. Epub 2018 Sep 25.

School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Republic of South Africa.

All domesticated mammals exhibit marked reductions in overall brain size, however, it is unknown whether the corpus callosum (CC), an integral white matter fiber pathway for interhemispheric cortical communication, is affected by domestication differentially or strictly in coordination with changes in brain size. To answer this question, we used quantitative magnetic resonance imaging to compare the midsagittal cross-sectional areas of the CC in 35 carnivore species, including eight wild canids and 13 domestic dogs. We segmented rostro-caudal regions of interest for the CC and evaluated correlations with brain mass. The results of this study indicate that under the influence of domestication in canids, the CC scales to brain size in an allometric relationship that is similar to that of wild canids and other carnivores, with relatively high correlation coefficients observed for all regions, except the rostrum. These results indicate that architectural and energetic considerations are likely to tightly constrain variation in caudal components of the CC relative to overall brain size, however fibers passing through the rostrum, putatively connecting prefrontal cortex, are less constrained and therefore may contribute more toward species-specific differences in connectivity. Given the species diversity of the Canidae and the resurgence of interest in the brain of the domestic dog, further studies aimed at characterizing the neural architecture in domesticated species is likely to provide new insights into the effects of domestication, or artificial selection, on the brain.
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http://dx.doi.org/10.1002/cne.24486DOI Listing
October 2018

PEDIATRIC RETINAL DETACHMENT IN AN ASIAN POPULATION WITH HIGH PREVALENCE OF MYOPIA: Clinical Characteristics, Surgical Outcomes, and Prognostic Factors.

Retina 2019 Sep;39(9):1751-1760

Surgical Retina Department, Singapore National Eye Centre, Singapore, Singapore.

Purpose: To evaluate the clinical characteristics and surgical outcomes of pediatric retinal detachments (RDs) in an Asian population.

Methods: Retrospective review of 171 eyes of 152 pediatric patients with rhegmatogenous RD over a 20-year period.

Results: Myopia was the most common risk factor in our population. At 6 months, primary anatomical success was 60.7%, and overall anatomical success was 86.7%. A total of 46.8% had best-corrected visual acuity of 20/40 or better, and 81.6% had best-corrected visual acuity of 20/200 or better. In primary RDs, high myopia (≤-6D) patients had a lower primary anatomical success compared to patients with moderate myopia (≤-2D) (59.3 vs. 100% P = 0.03). Increasing age and absence of proliferative vitreoretinopathy were associated with anatomical and visual success. Pars plana vitrectomy as the primary procedure was associated with decreased odds of anatomical success. A longer duration of symptoms, cataract, and a larger RD extent were associated with poorer functional outcome.

Conclusion: Myopia was the commonest risk factor for pediatric RD in our population. Good anatomical and functional outcome can be achieved with surgery. Increasing age at presentation and absence of proliferative vitreoretinopathy was associated with anatomical and functional success. High myopia was associated with poorer anatomical and functional outcome.
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http://dx.doi.org/10.1097/IAE.0000000000002238DOI Listing
September 2019

Comparison of diurnal blood pressure and urine production between people with and without chronic spinal cord injury.

Spinal Cord 2018 09 2;56(9):847-855. Epub 2018 Mar 2.

Department of Clinical Pharmacology, Austin Hospital, Heidelberg, VIC, Australia.

Study Design: Observational study.

Objectives: To quantify diurnal blood pressure (BP) patterns and nocturnal hypertension and to measure diurnal urine production in people with chronic spinal cord injury (SCI), compared with controls without SCI.

Setting: Chronic SCI population in the community in Victoria, Australia.

Methods: Participants were recruited by advertisement, and sustained SCI at least a year prior or were healthy able-bodied volunteers. Participants underwent ambulatory BP monitoring (ABPM), measurement of urine production, and completed questionnaires regarding orthostatic symptoms. Comparisons were made between participants with tetraplegia or paraplegia and able-bodied controls. Participants with night:day systolic BP < 90% were classified as dippers, 90-100% as nondippers, and >100% as reverse dippers.

Results: Groups with tetraplegia (n = 51) and paraplegia (n = 33) were older (42.1 ± 15 and 41.1 ± 15 vs. 32.4 ± 13 years, mean ± s.d.) and had a higher prevalence of males (88 and 85% vs. 60%) than controls (n = 52). The average BP was 110.8 ± 1.5/64.4 ± 1.2 mmHg, 119.4 ± 2.1/69.8 ± 1.5 mmHg, and 118.1 ± 1.4/69.8 ± 1.0 mmHg in tetraplegia, paraplegia, and controls, respectively. Of participants with tetraplegia, paraplegia and controls, reverse dipping was observed in 45, 13, and 2% (p < 0.001), while nocturnal hypertension was observed in 13, 23, and 18%, respectively (p = 0.48). A reduction in nocturnal urine flow rate compared with the day was observed in paraplegia and controls, but not tetraplegia.

Conclusions: Similar to the effects of acute SCI, chronic SCI, specifically tetraplegia, also causes isolated nocturnal hypertension, reverse dipping, orthostatic intolerance, and nocturnal polyuria. Cardiovascular risk management and assessment of orthostatic symptoms should include ABPM.
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http://dx.doi.org/10.1038/s41393-018-0081-3DOI Listing
September 2018

Frontal and temporal cortical volume, white matter tract integrity, and hemispheric asymmetry in schizotypal personality disorder.

Schizophr Res 2018 07 14;197:226-232. Epub 2018 Feb 14.

VISN 2 Mental Illness Research, Education, and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abnormalities in temporal and frontal cortical volume, white matter tract integrity, and hemispheric asymmetry have been implicated in schizophrenia-spectrum disorders. Schizotypal personality disorder can provide insight into vulnerability and protective factors in these disorders without the confounds associated with chronic psychosis. However, multimodal imaging and asymmetry studies in SPD are sparse. Thirty-seven individuals with SPD and 29 healthy controls (HC) received clinical interviews and 3T magnetic resonance T1-weighted and diffusion tensor imaging scans. Mixed ANOVAs were performed on gray matter volumes of the lateral temporal regions involved in auditory and language processing and dorsolateral prefrontal cortex involved in executive functioning, as well as fractional anisotropy (FA) of prominent white matter tracts that connect frontal and temporal lobes. In the temporal lobe regions, there were no group differences in volume, but SPD had reduced right>left middle temporal gyrus volume asymmetry compared to HC and lacked the right>left asymmetry in the inferior temporal gyrus volume seen in HC. In the frontal regions, there were no differences between groups on volume or asymmetry. In the white matter tracts, SPD had reduced FA in the left sagittal stratum and superior longitudinal fasciculus, and increased right>left asymmetry in sagittal stratum FA compared to HC. In the SPD group, lower left superior longitudinal fasciculus FA was associated with greater severity of disorganization symptoms. Findings suggest that abnormities in structure and asymmetry of temporal regions and frontotemporal white matter tract integrity are implicated in SPD pathology.
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http://dx.doi.org/10.1016/j.schres.2018.01.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043048PMC
July 2018

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

JAMA 2017 12;318(22):2211-2223

Singapore Eye Research Institute, Singapore National Eye Center, Singapore.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases.

Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes.

Design, Setting, And Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes.

Exposures: Use of a deep learning system.

Main Outcomes And Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard.

Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images).

Conclusions And Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.
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http://dx.doi.org/10.1001/jama.2017.18152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820739PMC
December 2017

Long-Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke.

J Am Heart Assoc 2017 Dec 7;6(12). Epub 2017 Dec 7.

Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong

Background: This study was performed to determine the clinical correlates and long-term prognostic implications of microbleed burden and location in Chinese patients with ischemic stroke.

Methods And Results: We recruited 1003 predominantly Chinese patients with ischemic stroke who received magnetic resonance imaging at the University of Hong Kong. We determined the clinical correlates of microbleeds and the long-term risks (3126 patient-years of follow-up) of recurrent ischemic stroke and intracerebral hemorrhage (ICH) by microbleed burden (0 versus 1, 2-4, and ≥5) and location, adjusting for age, sex, and vascular risk factors and stratified by antithrombotic use. Microbleeds were present in 450 of 1003 of the study population (119/450 had ≥5, 187/450 had mixed location). Having ≥5 microbleeds was independently associated with prior antiplatelet and anticoagulant use, whereas microbleeds of mixed location were independently associated with hypertension and prior anticoagulant use (all <0.05). Microbleed burden was associated with an increased risk of ICH (microbleed burden versus no microbleeds: 1 microbleed: multivariate hazard ratio: 0.59 [95% confidence interval, 0.07-5.05]; 2-4 microbleeds: multivariate hazard ratio: 2.14 [95% confidence interval, 0.50-9.12]; ≥5 microbleeds: multivariate hazard ratio: 9.51 [95% confidence interval, 3.25-27.81]; <0.0001), but the relationship of microbleed burden and risk of recurrent ischemic stroke was not significant (=0.054). Similar findings were noted in the 862 of 1003 patients treated with antiplatelet agents only (ICH: <0.0001; ischemic stroke =0.096). Multivariate analysis revealed that, independent of vascular risk factors, antithrombotic use, and other neuroimaging markers of small vessel disease, having ≥5 microbleeds (multivariate hazard ratio: 6.08 [95% confidence interval, 1.11-33.21]; =0.037) was identified as an independent predictor of subsequent ICH, but neither microbleed burden nor location was predictive of recurrent ischemic stroke risk.

Conclusions: In Chinese patients with ischemic stroke, a high burden of cerebral microbleeds was significantly associated with an increased risk of ICH; however, neither microbleed location nor burden was associated with recurrent ischemic stroke risk.
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http://dx.doi.org/10.1161/JAHA.117.007360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779045PMC
December 2017

Choroidal Remodeling in Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy: A 12-month Prospective Study.

Sci Rep 2017 08 11;7(1):7868. Epub 2017 Aug 11.

Singapore Eye Research Institute, Singapore National Eye Center 11 Third Hospital Avenue, Singapore, 168751, Singapore.

Choroid thinning occurs in age-related macular degeneration (AMD). However, it remains unclear whether the reduction is due to reduction in choroidal vessels or shrinkage of choroidal stroma, or both. The purpose of this study was to evaluate the changes of the choroidal vascular and stromal area in 118 patients with typical AMD (t-AMD) and polypoidal choroidal vasculopathy (PCV) over a 12-month period. We used spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode to measure the subfoveal choroidal thickness (CT), central retinal thickness (CRT) and choroidal vascularity index (CVI - ratio of luminal area to total choroidal area). At baseline, PCV eyes had higher CRT (471.6 µm vs 439.1 µm, p = 0.02), but comparable subfoveal CT and CVI, compared to t-AMD. Eyes with high CVI at baseline showed marked reduction in stromal area compared with eyes with average or low CVI. Over 12 months, CRT and subfoveal CT significantly decreased (p < 0.001) in both subtypes. Eyes with high baseline CVI showed significant CVI reduction from baseline to month 12 (p < 0.001), whereas eyes with average to low baseline CVI showed increase in CVI. These differences in choroidal vascularity may reflect different predominant pathogenic processes and remodeling in AMD eyes with varying spectrum.
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http://dx.doi.org/10.1038/s41598-017-08276-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554201PMC
August 2017

Blast Exposure, White Matter Integrity, and Cognitive Function in Iraq and Afghanistan Combat Veterans.

Front Neurol 2017 21;8:127. Epub 2017 Apr 21.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

The long-term effects of blast exposure are a major health concern for combat veterans returning from the recent conflicts in Iraq and Afghanistan. We used an optimized diffusion tensor imaging tractography algorithm to assess white matter (WM) fractional anisotropy (FA) in blast-exposed Iraq and Afghanistan veterans ( = 40) scanned on average 3.7 years after deployment/trauma exposure. Veterans diagnosed with a blast-related mild traumatic brain injury (mTBI) were compared to combat veterans with blast exposure but no TBI diagnosis. Blast exposure was associated with decreased FA in several WM tracts. However, total blast exposure did not correlate well with neuropsychological testing performance and there were no differences in FA based on mTBI diagnosis. Yet, veterans with mTBI performed worse on every neurocognitive test administered. Multiple linear regression across all blast-exposed veterans using a six-factor prediction model indicated that the amount of blast exposure accounted for 11-15% of the variability in composite FA scores such that as blast exposure increased, FA decreased. Education accounted for 10% of the variability in composite FA scores and 25-32% of FA variability in the right cingulum, such that as level of education increased, FA increased. Total blast exposure, age, and education were significant predictors of FA in the left cingulum. We did not find any effect of post-traumatic stress disorder on cognition or composite FA. In summary, our findings suggest that greater total blast exposure is a contributing factor to poor WM integrity. While FA was not associated with neurocognitive performance, we hypothesize that FA changes in the cingulum in veterans with multiple combat exposures and no head trauma prior to deployment may represent a marker of vulnerability for future deficits. Future work needs to examine this longitudinally.
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http://dx.doi.org/10.3389/fneur.2017.00127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399028PMC
April 2017

History of EPI Suite™ and future perspectives on chemical property estimation in US Toxic Substances Control Act new chemical risk assessments.

Environ Sci Process Impacts 2017 Mar;19(3):203-212

Abt Associates, Bethesda, MD 20814, USA.

Chemical property estimation is a key component in many industrial, academic, and regulatory activities, including in the risk assessment associated with the approximately 1000 new chemical pre-manufacture notices the United States Environmental Protection Agency (US EPA) receives annually. The US EPA evaluates fate, exposure and toxicity under the 1976 Toxic Substances Control Act (amended by the 2016 Frank R. Lautenberg Chemical Safety for the 21 Century Act), which does not require test data with new chemical applications. Though the submission of data is not required, the US EPA has, over the past 40 years, occasionally received chemical-specific data with pre-manufacture notices. The US EPA has been actively using this and publicly available data to develop and refine predictive computerized models, most of which are housed in EPI Suite™, to estimate chemical properties used in the risk assessment of new chemicals. The US EPA develops and uses models based on (quantitative) structure-activity relationships ([Q]SARs) to estimate critical parameters. As in any evolving field, (Q)SARs have experienced successes, suffered failures, and responded to emerging trends. Correlations of a chemical structure with its properties or biological activity were first demonstrated in the late 19 century and today have been encapsulated in a myriad of quantitative and qualitative SARs. The development and proliferation of the personal computer in the late 20 century gave rise to a quickly increasing number of property estimation models, and continually improved computing power and connectivity among researchers via the internet are enabling the development of increasingly complex models.
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http://dx.doi.org/10.1039/c7em00064bDOI Listing
March 2017

DETAILED CHARACTERIZATION OF CHOROIDAL MORPHOLOGIC AND VASCULAR FEATURES IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY.

Retina 2017 Dec;37(12):2269-2280

Singapore Eye Research Institute and Singapore National Eye Centre, Vitreo-Retinal Department, Singapore.

Purpose: To characterize and compare morphologic and vascular features of the choroid in patients with typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) and to determine if PCV subtypes can be identified based on these choroidal features.

Methods: Choroidal features of patients with AMD and PCV recruited from the prospectively planned Asian AMD Phenotyping Study were analyzed. Patients underwent choroidal imaging using spectral-domain optical coherence tomography with enhanced depth imaging. Raw optical coherence tomographic images were loaded on a custom-written application on MATLAB that enabled delineation for detailed morphologic and vascular analyses, including the curvature of the choroid-sclera interface, number of inflection points, choroidal thickness and choroidal vascular area within the macular (6 mm centered on fovea) and foveal (1.5 mm centered on fovea) regions. An inflection point represents the contour of the choroid-sclera interface, with >1 point signaling irregular shape.

Results: A total of 156 eyes of 156 patients (78 affected eyes of 78 patients with typical AMD and 78 affected eyes of 78 patients with PCV) were analyzed. Eyes with PCV had thicker baseline choroidal thickness and greater choroidal vascular area compared with those with typical AMD (P < 0.05); these differences were no longer significant after adjusting for age and hypertension (P > 0.05). Typical PCV subtype with choroidal thickness of ≥257 μm had significantly greater choroidal vascular area at macular (mean difference = 0.054 mm; P < 0.001) and foveal (mean difference = 0.199 mm; P < 0.001) regions compared with eyes with typical AMD. However, eyes with PCV without thick choroid had similar choroidal vascular area as eyes with typical AMD.

Conclusion: Based on the choroidal vascular features, two subtypes of PCV can be classified: typical PCV with increased choroid vascularity and polypoidal choroidal neovascularization with low choroidal vascularity. These data provide further understanding of different AMD and PCV subtypes.
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http://dx.doi.org/10.1097/IAE.0000000000001481DOI Listing
December 2017

Ketamine Treatment and Global Brain Connectivity in Major Depression.

Neuropsychopharmacology 2017 May 8;42(6):1210-1219. Epub 2016 Sep 8.

Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Capitalizing on recent advances in resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) and the distinctive paradigm of rapid mood normalization following ketamine treatment, the current study investigated intrinsic brain networks in major depressive disorder (MDD) during a depressive episode and following treatment with ketamine. Medication-free patients with MDD and healthy control subjects (HC) completed baseline rs-fcMRI. MDD patients received a single infusion of ketamine and underwent repeated rs-fcMRI at 24 h posttreatment. Global brain connectivity with global signal regression (GBCr) values were computed as the average of correlations of each voxel with all other gray matter voxels in the brain. MDD group showed reduced GBCr in the prefrontal cortex (PFC) but increased GBCr in the posterior cingulate, precuneus, lingual gyrus, and cerebellum. Ketamine significantly increased GBCr in the PFC and reduced GBCr in the cerebellum. At baseline, 2174 voxels of altered GBCr were identified, but only 310 voxels significantly differed relative to controls following treatment (corrected α<0.05). Responders to ketamine showed increased GBCr in the lateral PFC, caudate, and insula. Follow-up seed-based analyses illustrated a pattern of dysconnectivity between the PFC/subcortex and the rest of the brain in MDD, which appeared to normalize postketamine. The extent of the functional dysconnectivity identified in MDD and the swift and robust normalization following treatment suggest that GBCr may serve as a treatment response biomarker for the development of rapid acting antidepressants. The data also identified unique prefrontal and striatal circuitry as a putative marker of successful treatment and a target for antidepressants' development.
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http://dx.doi.org/10.1038/npp.2016.186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437875PMC
May 2017

A surprising visual improvement following a prolonged 5-month retained subfoveal perfluorocarbon liquid.

Int J Ophthalmol 2016 18;9(7):1079-81. Epub 2016 Jul 18.

Singapore National Eye Center, 11 Third Hospital Avenue, 168751, Singapore.

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http://dx.doi.org/10.18240/ijo.2016.07.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951667PMC
August 2016

Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder.

Hum Brain Mapp 2016 09 4;37(9):3214-23. Epub 2016 May 4.

Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity.

Methods: A total of 82 subjects, including medication-free patients with major depression (n = 57) and healthy volunteers (n = 25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel's time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation.

Results: Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges' g = -1.48, P < 0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = -0.47, P = 0.0005).

Conclusions: Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. Hum Brain Mapp 37:3214-3223, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980239PMC
September 2016

Cortical abnormalities and association with symptom dimensions across the depressive spectrum.

J Affect Disord 2016 Jan 30;190:529-536. Epub 2015 Oct 30.

Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY, United States; Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address:

Background: Few studies have investigated the relationship between structural brain abnormalities and dimensions of depressive symptomatology.

Methods: In the current study, we examined the relationship between cortical structural abnormalities and specific behavioral dimensions relevant to depression in a sample of unmedicated patients with major depressive disorder (MDD, n=57) and demographically similar healthy control volunteers (HC, n=29). All subjects underwent diagnostic assessment with the SCID, MRI at 3T, and dimensional assessments using the visual analog scales (VAS). Cortical regions were extracted for each subject, and group comparisons of cortical volume (CV), surface area (SA), and cortical thickness (CT) were performed controlling for multiple comparisons using a bootstrapping technique. Regions demonstrating group differences were analyzed for correlation with specific dimensions assessments.

Results: As compared with HC, MDD subjects exhibited reduced CV within the left supramarginal gyrus, right ventrolateral prefrontal cortex (VLPFC), entorhinal cortex, parahippocampal gyrus, fusiform gyrus and pericalcarine; reduced SA in the right VLPFC, cuneus, and left temporal pole; and reduced CT in the right rostral anterior cingulate cortex (rACC) (all p's<0.05, corrected). The largest effect occurred within the right VLPFC for CV and SA (MDD
Limitations: Future studies will be required to further map the anatomical changes in depression to behavioral dimensions.

Conclusions: Our results indicate that specific cortical abnormalities are associated with specific behavioral components linked to depression.
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http://dx.doi.org/10.1016/j.jad.2015.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764252PMC
January 2016

MYOPIC RETINOSCHISIS IN ASIANS: Structural Features and Determinants of Visual Acuity and Prognostic Factors for Progression.

Retina 2016 Apr;36(4):717-26

*Singapore National Eye Center, Department of Ophthalmology, Tan Tock Seng Hospital, Singapore, Singapore; †Singapore National Eye Centre, Singapore, Singapore; ‡Singapore Eye Research Institute, Singapore, Singapore; §Ophthalmology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore; and ¶Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Purpose: To describe microstructural changes and schisis extent in eyes with myopic retinoschisis and to determine their influence on visual acuity at baseline and follow-up.

Methods: In this prospective observational study, 50 eyes of 38 patients with myopic retinoschisis were evaluated using spectral domain optical coherence tomography, and the patients were followed for at least 12 months. The presence of microstructural changes and the extent of retinoschisis at baseline on spectral domain optical coherence tomography, and the association between these parameters and the risk of visual acuity deterioration were analyzed.

Results: Median presenting visual acuity and central retinal thickness were 0.31 logMAR (≈20/40) and 395 μm, respectively. Twenty-six eyes (52%) had entire macular area retinoschisis. Common microstructural changes included photoreceptor detachment (24%), foveal ellipsoid zone (EZ) disruption (34%), partial-thickness macular hole (26%), and full-thickness macular hole (16%). Visual acuity was poorer in eyes with photoreceptor detachment, EZ disruption, full-thickness macular hole, and central retinal thickness >300 μm. Eyes with entire macular area retinoschisis had the poorest visual acuity and thickest central retinal thickness, and they were more likely to have photoreceptor detachment, EZ disruption, and retinal detachment. Over a mean follow-up of 31.7 ± 7.7 months, 14 eyes (28%) had worsening visual acuity of ≥2 lines. Ten of these 14 eyes had entire macular retinoschisis at baseline.

Conclusion: Most eyes with myopic retinoschisis remain stable. However, eyes with extensive retinoschisis involving the entire macular area are more likely to progress and have microstructural abnormalities and poorer vision. Early surgery should be considered for these eyes.
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http://dx.doi.org/10.1097/IAE.0000000000000757DOI Listing
April 2016

Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab.

Clin Ophthalmol 2015 16;9:1715-8. Epub 2015 Sep 16.

Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.

Background: The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept.

Methods: This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept.

Results: In total, 21 eyes from 19 subjects of mean age 62±15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52±143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57±92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17±98.76 mm (P<0.001). Mean visual acuity was 0.42±0.23 logMAR just prior to the switch, 0.39±0.31 logMAR after one aflibercept injection, and 0.37±0.22 log-MAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04).

Conclusion: Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept.
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http://dx.doi.org/10.2147/OPTH.S81523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577250PMC
September 2015

Prognostic factor analysis of vitrectomy for myopic foveoschisis.

Br J Ophthalmol 2015 Dec 2;99(12):1639-43. Epub 2015 Jul 2.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore Duke-NUS Graduate Medical School.

Purpose: To describe the anatomical and functional outcomes in a cohort of subjects undergoing vitrectomy for myopic foveoschisis, and to analyse the factors predicting foveal reattachment and visual improvement.

Methods: This retrospective case series evaluated case records and optical coherence tomography images 6 months after surgery. Multivariate linear and logistic regressions were performed to assess the factors predicting anatomical and visual improvement.

Results: In total, 55 eyes of 54 patients were analysed. The mean spherical equivalent refraction was -11.83±4.94D. Foveal detachment was present in 63.5% of eyes preoperatively and subjects with foveal detachment had 0.70 logMAR units (95% CI 0.02 to 1.39) poorer visual acuity than subjects without (p=0.046). The mean preoperative visual acuity was 0.84±0.59 logMAR units and the mean postoperative visual acuity was 0.64±0.64 logMAR units (mean difference 0.20±0.68 logMAR units (p=0.04)). The proportion of eyes with foveal detachment was significantly lower after surgery (12.5%; p<0.001). However, the proportion of eyes with ellipsoid zone disruption was significantly higher after surgery (59.6% vs 34.0%; p<0.001). In multivariate analyses, the preoperative central foveal thickness significantly predicted postoperative visual improvement by two or more lines (OR 1.004 (95% CI 1.000 to 1.007), per μm increase; p=0.049). The presence of ellipsoid zone disruption preoperatively was associated with 0.96 logMAR (95% CI 0.2 to 1.72) poorer final acuity (p=0.02).

Conclusions: Eyes with myopic foveoschisis with preoperative ellipsoid disruption and thinner central foveal thickness tend to have poorer visual outcomes. While current surgical manoeuvres are effective in reattaching the fovea, they may also cause iatrogenic injury to the photoreceptors.
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http://dx.doi.org/10.1136/bjophthalmol-2015-306885DOI Listing
December 2015

IMPROVED SPECIFICITY OF POLYPOIDAL CHOROIDAL VASCULOPATHY DIAGNOSIS USING A MODIFIED EVEREST CRITERIA.

Retina 2015 Jul;35(7):1375-80

*Medical Retina Service, Singapore National Eye Center, Singapore, Singapore; †Singapore Eye Research Institute, Singapore, Singapore; ‡Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; §Academic Clinical Program in Ophthalmology and Visual Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore; and ¶National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, Singapore.

Purpose: To evaluate the performance of polypoidal choroidal vasculopathy (PCV) diagnosis using fundus camera-based indocyanine green angiography, comparing a single sign of "subretinal focal hyperfluorescence" on indocyanine green angiography with a modification of the EVEREST criteria.

Methods: Color fundus photograph, flash fundus camera-based fluorescein angiography, and indocyanine green angiography of 241 eyes of 230 consecutive patients with exudative maculopathy due to PCV or typical age-related macular degeneration were graded independently by 2 retinal specialists using a modified EVEREST criteria, which requires the presence of subretinal focal hyperfluorescence plus any 1 of 5 additional criteria. Discordant cases were adjudicated by a senior retinal specialist to arrive at the final diagnosis. Sensitivity, specificity, and area under the receiver operating curve of subretinal focal hyperfluorescence versus the EVEREST criteria and combinations of individual EVEREST criteria were compared.

Results: Among the 241 eyes with exudative maculopathy, 131 eyes had PCV and 110 eyes had typical age-related macular degeneration. Using a single sign of subretinal focal hyperfluorescence alone for the diagnosis of PCV, sensitivity was 85.3% and specificity was 80.9%, with an area under the receiver operating curve of 83.1%. When applying the EVEREST definition, sensitivity was reduced to 78.4% but specificity improved to 87.1% with a similar area under the receiver operating curve of 82.8%. The frequency of individual criteria was highly variable, with stereo nodular appearance (73.7%) and orange nodule (55.0%) being the most common and branching vascular network, massive hemorrhage, and hypofluorescent halo in the presence of subretinal focal hyperfluorescence being less common (21.5%-28.1%).

Conclusion: The EVEREST criteria have a higher specificity for the diagnosis of PCV than subretinal focal hyperfluorescence alone and may be applied to flash fundus camera-based indocyanine green angiography in a clinical setting. Stereo nodular appearance is the most important additional criterion.
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http://dx.doi.org/10.1097/IAE.0000000000000482DOI Listing
July 2015

SCLERAL BUCKLING VERSUS VITRECTOMY IN THE MANAGEMENT OF MACULA-OFF PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A COMPARISON OF VISUAL OUTCOMES.

Retina 2015 Dec;35(12):2552-7

*Singapore National Eye Centre, Vitreoretinal Service, Singapore, Singapore; and †Singapore Eye Research Institute, Singapore, Singapore.

Purpose: To compare visual outcomes between pars plana vitrectomy (PPV) with or without scleral buckling (SB) and SB alone in the management of uncomplicated macula-off primary rhegmatogenous retinal detachment.

Methods: Case-control study of 723 patients with uncomplicated macula-off primary rhegmatogenous retinal detachment seen at the Singapore National Eye Centre from 2005 to 2011. The primary outcome measure was the proportion of eyes achieving functional success, defined as logMAR best-corrected visual acuity of ≤0.3 logMAR at 6 months postoperatively. Multivariable logistic regression analysis was performed adjusting for the following preoperative covariates: age, gender, race, lens status, number of tears found, presence of proliferative vitreoretinopathy, operative procedure, logMAR best-corrected visual acuity, and duration of symptoms.

Results: Three hundred and eight eyes underwent SB alone, and 415 eyes underwent PPV ± SB. In the SB group, 133 eyes (43.2%) achieved functional success compared with 116 eyes (28.0%) in the PPV ± SB group. This difference was statistically significant on both univariate (P < 0.001) and multivariable analyses (OR: 1.51, 95% CI: 1.03-2.21, P = 0.03).

Conclusion: Scleral buckling alone may achieve visual outcomes that are at least comparable with PPV ± SB in the management of macula-off primary rhegmatogenous retinal detachment.
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http://dx.doi.org/10.1097/IAE.0000000000000642DOI Listing
December 2015