Louis W. Lim

Topographic variation of choroidal and retinal thicknesses at the macula in healthy adults.

Background/aims To determine the topographic variation of macular choroidal and retinal thicknesses (RTs) in normal eyes and their relationship with refractive error. Methods Spectral domain optical coherence tomography with enhanced depth imaging was performed on 124 healthy participants using a standardised imaging protocol. Manual segmentation of choroidal boundaries was performed by trained graders, and mean choroidal thickness (CT) was compared with mean RT in corresponding sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Results Mean central subfield CT was 322.2u2005µm. The choroid was thickest at the temporal and superior sectors (323.1–338.1u2005µm), followed by inferior sectors (314.0–321.8u2005µm), and thinnest at the nasal sectors (232.8–287.8u2005µm). In contrast, the retina was thicker nasally (343.4u2005µm) and thinner temporally (287.1u2005µm). CT was thickest among emmetropes in all ETDRS subfields and became thinner progressively among low, moderate and high myopes (p<0.001). The variation of both choroidal and RTs among refractive error groups resulted in different topographic patterns at the macula. Conclusion There is significant topographic variation of choroidal and RTs at different regions of the macula, with progressive change of choroidal thickness in all sectors based on the refractive status of the eye.

A novel classification of the vascular patterns of polypoidal choroidal vasculopathy and its relation to clinical outcomes.

Purpose To propose a novel classification system for polypoidal choroidal vasculopathy (PCV), and compare the clinical outcomes among PCV subtypes. Methods Consecutive treatment-naive patients with symptomatic PCV were managed over 5u2005years. PCV subtypes were classified based on indocyanine green angiography (ICGA) and fluorescein angiography (FA) characteristics. Results Among 107 patients, 3 PCV subtypes were seen: Type A (interconnecting channels on ICGA) –22.4%; Type B (branching vascular network with no leakage) –24.3%; Type C (branching vascular network with late leakage on FA) –53.3%. The proportion of patients with best-corrected visual acuity (BCVA) ≥20/40 was highest in Type A, intermediate in Type B and lowest in Type C at all time points (80% vs 66.7% vs 7.7% at 5u2005years, p<0.001). The highest rate of moderate visual loss (loss of ≥3 lines) occurred in Type C PCV (57.7% vs 0% for Types B and A at 5u2005years, p<0.001). Risk factors for poor visual outcomes were PCV subtype (OR 53.7, p<0.001 for Type C and OR 13.7, p=0.023 for Type B compared to Type A) and age (OR 1.06, 95% CI 1.002 to 1.125, p=0.044). Conclusions The PCV subtype seen on initial presentation affects the long-term visual outcomes over a 5-year period.

Optical Coherence Tomography Angiography Evaluation of the Parafoveal Vasculature and Its Relationship With Ocular Factors

PURPOSEnTo determine the size and characteristics of the superficial and deep foveal avascular zone (FAZ) in healthy adults by using optical coherence tomography angiography (OCT-A), and to ascertain the effects of demographic and ocular parameters on the FAZ size.nnnMETHODSnIn a prospective cohort study of 117 healthy volunteers, foveal-centered 3 × 3-mm OCT-A scans were manually graded by certified graders to determine the size of the superficial and deep FAZ. Multiple linear regression analyses were performed to evaluate the impact of demographics and ocular factors, including central retinal thickness (CRT), choroidal thickness, axial length (AL), and spherical equivalent (SE) on superficial and deep FAZ areas.nnnRESULTSnThe mean age of the participants was 22.5 years, with mean AL of 25.4 mm and mean SE of -4.3 diopters. The mean CRT was 262.8 μm (range, 220-316 μm). The mean superficial FAZ area was 0.24 mm2, while the deep FAZ area was 0.38 mm2 (P < 0.001). Females had a larger superficial (P < 0.001) and deep FAZ (P < 0.001). On univariate linear regression, both superficial and deep FAZ areas had significant correlations with CRT, sex, AL, and SE, but not with age. By multiple linear regression analysis, in normal eyes, superficial FAZ area varied significantly with CRT and sex. Among eyes with high myopia, both superficial and deep FAZ varied significantly with CRT, sex, and choroidal thickness.nnnCONCLUSIONSnThe superficial and deep FAZ areas varied significantly among healthy eyes. Factors such as CRT, sex, SE, AL, and choroidal thickness influence the size of the FAZ.

Comparison of macular choroidal thicknesses from swept source and spectral domain optical coherence tomography.

Background Choroidal thickness (CT) measurements differ between swept source optical coherence tomography (SS-OCT) and spectral domain OCT (SD-OCT) devices for point thickness measurements. We aimed to assess the comparability of mean macular CT measurements between SS-OCT and SD-OCT devices. Methods In a prospective cohort study of 25 healthy volunteers, OCT scans were performed sequentially with the deep range imaging (DRI) OCT-1 and Spectralis OCT using standardised imaging protocols. These OCT scans were independently graded by reading centre-certified graders to obtain mean CT in the various Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Paired t tests and intraclass correlation coefficients (ICCs) were used to compare the measurements. Results The difference in mean central subfield CT between DRI OCT-1 and Spectralis was 49.3u2005µm (p<0.001), while differences in CT in various ETDRS subfields varied from 42.1 to 67.2u2005µm. After manual adjustment of the segmentation boundaries for the central subfield in the DRI OCT-1, the mean central subfield CT for DRI OCT-1 increased from 263.1 to 293.3u2005µm (p<0.001), and the resultant difference between DRI OCT-1 and Spectralis decreased from 49.3 to 19.1u2005µm (a decrease of 61.3%; p<0.001). CT between the three-dimensional and radial scanning protocols of the DRI OCT-1 were highly comparable, with differences generally under 10u2005µm and ICC of 0.888 for the central subfield. Conclusions CT measurements between automated segmentations from the DRI OCT-1 and manual segmentations on the Spectralis OCT may differ by more than 50u2005µm. This difference can be reduced, but not eliminated, by manual adjustment of segmentation boundaries by trained graders, and should be accounted for when comparing results between the two devices.

EVEREST study report 3: diagnostic challenges of polypoidal choroidal vasculopathy. Lessons learnt from screening failures in the EVEREST study

PurposeTo describe screening failures in the EVEREST study by examining the imaging characteristics that enabled differentiation of polypoidal choroidal vasculopathy (PCV) from cases that were subsequently diagnosed not to be PCV.MethodsPost-hoc analysis of 34 patients with PCV reported as screening failures from EVEREST study. Standardised confocal scanning laser indocyanine green angiography (ICGA) images were graded by the Central Reading Centre to confirm PCV diagnosis based on the presence of early focal sub-retinal hyperfluorescence on ICGA and at least one of the following six diagnostic criteria: (1) nodular appearance of polyp(s) on stereoscopic examination, (2) hypofluorescent halo around nodule(s), (3) presence of a branching vascular network, (4) pulsation of polyp(s) on dynamic ICGA, (5) orange sub-retinal nodules on colour fundus photography, or (6) massive sub-macular haemorrhage (≥4 disc areas in size). Additional detailed image grading was performed with stereo-imaging and dynamic early-phase ICGA.ResultsOf the 95 screened PCV cases, 34 were excluded: (1) cases not suitable for recruitment as per the study protocol (nu2009=u200914), (2) equivocal lesions on ICGA characterised by small hyperfluorescent dots (nu2009=u20099), and (3) cases that were definitely not PCV (non-PCV, nu2009=u200911), identified by definitive diagnoses which included one case each of micro-aneurysm, retinal angiomatous proliferation, retino-choroidal anastomosis, small type-2 choroidal neovascularisation, retinal pigment epithelial (RPE) window defect and disciform scar; two cases of lesions where the choroidal vessel changed its course; and three cases of late-onset RPE staining.ConclusionsStandardised image grading techniques used in EVEREST study enabled effective differentiation of non-PCV from actual PCV.

A randomized trial of intravitreal bevacizumab vs. ranibizumab for myopic CNV

AimsThe aim was to compare the efficacy of intravitreal therapy with bevacizumab and ranibizumab for choroidal neovascularization (CNV) in pathologic myopia (PM).MethodsThis was a prospective multicenter randomized nonblinded trial.ResultsIn seven centers, 78 eyes were randomized 1:1 to treatment with bevacizumab (group B, 40 eyes) or ranibizumab (group R, 38 eyes) given with an “on demand” regimen (PRN). The mean follow-up was 19xa0months (SD 2, range 12–24). The mean BCVA at baseline was 0.60 logMAR (20/80 Snellen equivalent, Seq) and 50 letter score (ls). Mean final BCVA was 0.51 LogMAR (20/63 Seq) and 57 ls (pu2009=u20090.0009 and pu2009=u20090.0002, respectively). In group B, mean basal BCVA was 0.52 logMAR (20/63 Seq) and 54 ls, and final BCVA was 0.51 logMar (20/63 Seq) and 57 ls. In group R, mean basal BCVA was 0.62 logMAR (20/80 Seq) and 45 ls, and the final values were 0.50 logMAR (20/63 Seq) and 58 ls. Statistical comparison of the two groups showed no significant difference (logMAR pu2009=u20090.90 and letters pu2009=u20090.78). Multivariate analysis showed no influence of age or previous photodynamic treatment (PDT) on final visual changes. The mean number of treatments in the first year was 2.7 in group B and 2.3 in group R (pu2009=u20090.09).ConclusionMyopic CNV equally benefits from on-demand intravitreal injection of either bevacizumab or ranibizumab; the therapeutic effect is independent of previous PDT and age.

Diurnal variation of retinal thickness measured by optical coherence tomography in normal adults.

We read with interest the article by Jo et al. in the August 2011 issue describing the diurnal variation of retinal thickness in normal subjects measured by time-domain (TD) and spectraldomain (SD) optical coherence tomography (OCT). The authors concluded that the diurnal variation in the retinal thickness observed with TD-OCT was caused by limitations in the repeatability of the OCT device rather than by actual variation of retinal thickness. Although this was a well-designed study, one limitation was that the retinal thickness was assessed at only two time points, which provides limited information on the pattern of diurnal change. A difference between two time points is less compelling than if the retinal thickness measurements differ across several additional points during the day. We would like to highlight two other studies in normal subjects that provide additional evidence to support the findings of Jo et al. A significant strength of both of the additional studies is that the retinal thickness was measured at five time points during a single day, thus providing more comprehensive and robust data for the analysis of diurnal variation compared with the two time points that were used in the present study. In addition, in both studies, the examination sequence (five OCT scans during the day) was repeated on a separate day to confirm the consistency of the results. In a study of 12 normal individuals, sequential SD-OCT scans were performed with the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). The authors found no significant variation in the macular thickness over the five time points during the day, with a maximum amplitude (the difference between the maximum and minimum retinal thickness) of 0.9 m. This result is comparable to the difference of 0.3 m reported by Jo et al. for central macular thickness measured with the Cirrus OCT (Carl Zeiss Meditec, Dublin, CA). In addition, this study used the tracking function of the Spectralis OCT to reduce the chance of a small displacement of the foveal B-scan position between sequential OCT scans and to ensure that the same point on the retina was measured for all OCT scans. We feel that this is a useful and important advantage, conferred by the tracking function of the Spectralis OCT. In another study, Chakraborty et al. 3 used an optical biometer instead of OCT to measure retinal thickness. They also reported no significant diurnal variation in retinal thickness (mean amplitude, 8 m) over the 2 days of examination. Another interesting point that merits discussion is that, in Jo et al., in the sectors that showed a significant difference in retinal thickness on TD-OCT, the mean difference ranged from 2.5 to 3.5 m. Although this difference may be statistically significant, it is unlikely to be of clinical relevance. In addition, the coefficient of repeatability of Stratus OCT retinal thickness in normal individuals has been reported to be approximately 17 m, which is much greater than the difference between the two time points in this study. Jo et al. also cited earlier studies that have reported diurnal variation in retinal thickness in patients with macular diseases. In these studies, various versions of TD-OCT were used to perform the OCT scans. Although it is certainly possible that the diurnal variation in retinal thickness may be due to the underlying disease process, it is also possible that at least part of it is due to motion artifact resulting from poor fixation as a result of the underlying disease process. It would be interesting to know whether a similar degree of diurnal change in retinal thickness in diseased eyes would be observed with tracking-capable SD-OCT devices. In summary, in confirming this finding using SD-OCT with tracking, we agree with Jo et al. that there does not appear to be significant diurnal variation in retinal thickness in normal individuals. Colin S. H. Tan Wei Kiong Ngo Milton C. Chew Kelvin Z. Li Louis W. Lim Srinivas R. Sadda

Validation study of WatchPat 200 for diagnosis of OSA in an Asian cohort

To validate a wrist-worn portable device (WatchPat 200) to diagnose OSA in an Asian cohort. To evaluate its cost-effectiveness. Twenty patients with suspected OSA were recruited and had simultaneous polysomnography (PSG) and WatchPAT assessments concurrently within the hospital’s sleep laboratory. The study population consisted of 18 male and 2 female patients, whose mean age was 39 (±16) years, mean BMI was 27.2 (±5.5)xa0kg/m2, mean Epworth Sleepiness score was 8.55 (±4.8). The correlation between the AHI was assessed using Spearman’s correlation coefficient and agreement was tested via the Bland Altman plot. Sensitivities and specificities were then applied to the various AHI groups. Spearman’s coefficient was 0.94, which suggested that a very strong correlation between the AHI recorded by the WatchPat and the PSG. Bland–Altman plot showed good agreement with the AHI mean difference of about 4.23 with a slight tendency to overscore the AHI at the mild range of OSA and underscore the range at the severe end of OSA. The WatchPat showed 100% sensitivity when compared to PSG for mild OSA and is thus a good screening test for the undiagnosed general population. Furthermore, it also showed 100% specificity when compared to PSG for severe OSA suggesting that it is a good diagnostic test for people with a high suspicion of OSA. This facilitates a timelier diagnosis and a more economical approach with potential cost savings of up to

Advances in retinal imaging for diabetic retinopathy and diabetic macular edema

900 per patient.

EVEREST Report 5: Clinical Outcomes and Treatment Response of Polypoidal Choroidal Vasculopathy Subtypes in a Multicenter, Randomized Controlled Trial

Diabetic retinopathy and diabetic macular edema (DME) are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA) detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT) provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease.