Wei Kiong Ngo

Comparison of choroidal thicknesses using swept source and spectral domain optical coherence tomography in diseased and normal eyes

Background/aims Choroidal thickness measurements are reported to differ between swept source optical coherence tomography (SS-OCT) and spectral domain OCT (SD-OCT). This study aimed to assess the comparability of choroidal thickness measurements using SS-OCT and SD-OCT devices among patients with retinal diseases and normal participants. Methods In a prospective cohort study of 100 subjects, comprising patients with retinal disease and normal volunteers, OCT scans were performed sequentially with the DRI OCT-1 and Spectralis OCT using standardised imaging protocols. Subfoveal choroidal thicknesses were independently measured by masked reading-centre certified graders. Paired t tests and intraclass correlation coefficients (ICCs) were used to compare the measurements. Results Among all 100 participants, mean subfoveal choroidal thickness was 264.3 µm and 272.4 µm for DRI OCT-1 and Spectralis OCT respectively (p=0.001), with ICC of 0.989. The mean difference in choroidal thickness between OCT devices was larger among eyes with retinal diseases compared with normal eyes (8.4 µm vs 7.3 µm). Eyes with choroidal thickness ≤200 µm had smaller differences between OCT devices compared with those with thicker choroids (mean 3.6 µm vs 10.0 µm, p=0.021). Conclusions Subfoveal choroidal thickness measurements are comparable between DRI OCT-1 and Spectralis OCT. The presence of retinal disease increases the variability of choroidal thickness measurements between OCT devices.

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 5 years. 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 5 years, 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 5 years, 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.

EVEREST study report 2: imaging and grading protocol, and baseline characteristics of a randomised controlled trial of polypoidal choroidal vasculopathy

Purpose To describe the imaging standards, grading protocol and baseline characteristics of polypoidal choroidal vasculopathy (PCV) from the EVEREST study. Methods In a prospective, multicentre study, confocal scanning laser ophthalmoscope indocyanine green angiography (ICGA) was performed using a standardised imaging protocol. All images were graded using standardised, calibrated equipment by fellowship-trained ophthalmologists at the Central Reading Center. Results Sixty-one patients with PCV were included in the study. ICGA characteristics included: nodular appearance stereoscopically (56 eyes, 91.8%), hypofluorescent halo (42, 68.9%), abnormal vascular network (54, 88.5%) and pulsation of the polyps (4, 6.6%). Colour fundus photography revealed orange subretinal nodules (34, 55.7%) and massive submacular haemorrhage (8, 13.1%). The mean area of the PCV lesion was 3.11 mm2 (range, 0.2–10.7 mm2). The vascular channels filled within 7.3–32.0 s (mean: 17.9 s) while the mean filling time for polyps was 21.9 s (range, 7.3–40.4 s). Patients with massive submacular haemorrhage were less likely to have abnormal vascular channels seen on ICGA (28.6% vs 83.3% for those without massive haemorrhage, p=0.001). Conclusions The imaging and grading protocols and baseline characteristics of a multicentre, randomised controlled trial of PCV are described in detail, and may serve as reference for future randomised, controlled trials on PCV. Clinical trial number This work was supported by Novartis Pharma AG, Basel, Switzerland grant number NCT00674323 (clinicaltrials.gov).

Comparison of retinal thicknesses measured using swept-source and spectral-domain optical coherence tomography devices.

BACKGROUND AND OBJECTIVE To compare retinal thicknesses measured using swept-source optical coherence tomography (SS-OCT) and spectral-domain (SD) OCT devices. PATIENTS AND METHODS In a cohort study of 76 healthy eyes and 21 eyes with high myopia, mean retinal thicknesses in ETDRS subfields were compared between OCT scans obtained from the Topcon DRI OCT-1 (Topcon, Tokyo, Japan), Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), and Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). RESULTS Central retinal thickness measurements differed significantly among the three OCT devices (Spectralis: 271 µm; Cirrus: 254 µm; DRI OCT-1: 238 µm; P < .001), with mean differences ranging from 15.6 µm to 37 µm. Intraclass correlation coefficients were at least 0.94 for any pair of machines. Similar results were observed in all nine ETDRS subfields. In all sectors, retinal thickness measurements obtained using the 3-D and radial scans of the SS-OCT were similar (mean differences: 0.7 to 3.8 µm). CONCLUSION Retinal thickness measurements obtained from DRI OCT-1 and SD-OCT are different and should be accounted for when comparing results of OCT scans from different 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 (n = 14), (2) equivocal lesions on ICGA characterised by small hyperfluorescent dots (n = 9), and (3) cases that were definitely not PCV (non-PCV, n = 11), 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.

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

Is age a risk factor for diabetic retinopathy

We read with interest the article by Namperumalsamy et al 1 describing the prevalence of diabetic retinopathy and its associated risk factors in a South Indian community. The authors reported that older age (>50 years) was a significant risk factor for the prevalence of diabetic retinopathy. This finding has potential ramifications in view of the increasing proportion of older people worldwide, who are more likely to develop and require treatment for diabetes and its complications. A review of …

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

Purpose The purpose of this study was to describe the characteristics of polypoidal choroidal vasculopathy (PCV) subtypes among patients from a multicenter randomized controlled trial and to determine the impact of PCV subtypes on clinical outcomes. Methods This was a prospective cohort study of 61 patients with macular PCV from the EVEREST study. Indocyanine green (ICGA) and fluorescein angiography (FA) obtained using standardized imaging protocols were graded to classify PCV into three subtypes. Type A PCV had polyps with interconnecting channels, type B had polyps with branching vascular networks, but no significant leakage on FA, and type C had polyps with branching vascular networks and leakage on FA. The best-corrected visual acuity (BCVA) and proportion of patients with BCVA ≥ 20/40 were compared among the three PCV subtypes. Results Of the 61 patients, 54 were gradable for PCV subtype. Among these, 8 had type A PCV (14.8%), 27 had type B (50%), and 19 had type C (35.2%). At baseline, BCVA was 67.1 letters for type A, 58.7 for type B, and 43.5 for type C (P < 0.001). At 6 months, BCVA was highest among patients with type A compared with types B and C (80.1 letters versus 67.2 versus 50.4, respectively; P < 0.001). Type A PCV gained 13 letters compared with 8.5 (type B) and 6.9 (type C). BCVA ≥ 20/40 was highest for type A compared with types B and C (100% vs. 51.9% vs. 10.5%; P < 0.001). On performing ANCOVA, PCV subtype and baseline BCVA significantly affected final BCVA. Conclusions The visual outcome following treatment varies with PCV subtype classification. The distinction in clinical outcomes between the PCV subtypes is observed in the initial months following the start of treatment.

Outcomes of polypoidal choroidal vasculopathy treated with ranibizumab monotherapy

We read with interest the article by Hikichi et al 1 describing the 2-year outcomes of intravitreal ranibizumab monotherapy for the treatment of patients with polypoidal choroidal vasculopathy (PCV). The authors reported significant improvement in visual acuity compared with baseline for both the first and second years, and a corresponding decrease in the mean foveal thickness measured on optical coherence tomography. While these results are indeed encouraging, we feel that it is important to discuss the frequency of polyp regression and its implications on the long-term prognosis of patients with PCV. In the current study, the proportion of eyes in which no polypoidal lesions were detected on indocyanine green angiography was 40% 1 year after the first injection and …

Polypoidal Choroidal Vasculopathy in patients diagnosed with age-related macular degeneration

Editor, W e congratulate Ilgninis and co-authors for their interesting article describing the prevalence of polypoidal choroidal vasculopathy (PCV) in a series of hospital patients in Denmark (Ilginis et al. 2012). While the prevalence of PCV in Western populations is generally reported to be lower than among Asians (Lim et al. 2010), the results reported by Ilginis et al. (2012) and other authors confirm that PCV is an important condition in Western populations, accounting for up to 10% of patients presenting as neovascular age-related macular degeneration (AMD) (Lim et al. 2010). We agree with the authors that the prevalence of PCV may be underdiagnosed in some populations and would like to stress the importance of indocyanine green angiography (ICGA) in the investigations of patients presenting with signs of neovascular AMD, especially if they have previously been treated and appear refractory to standard intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. There have been several reports of patients with presumed AMD who were unresponsive to anti-VEGF treatment. The diagnosis of PCV was subsequently confirmed when ICGA was performed (Cho et al. 2009; Stangos et al. 2010). It has been suggested that modifications in therapeutic protocols may be required to improve visual and anatomical outcomes in these patients (Cho et al. 2009). It is important to differentiate PCV from neovascular AMD because the EVEREST study (Koh et al. 2012) has demonstrated that the optimal treatment of PCV differs from AMD, with a higher rate of polyp closure achieved with combination therapy of photodynamic therapy (PDT) and anti-VEGF injections compared to treatment with anti-VEGF monotherapy. The EVERST study, however, only assessed outcomes up to 6 months. Some authors have suggested that repeated PDT monotherapy has limitations as a long-term treatment for PCV and suggested the concurrent use of anti-VEGF agents (Yuzawa 2012). The variability in visual outcomes of PDT treatment for PCV may be due to the existence of different subgroups of PCV. Yuzawa reported two subgroups of PCV, the first with both feeder and draining vessels, and network vessels showing characteristic findings of choroidal neovascularization (CNV) (Yuzawa 2012). The second pattern had neither feeder nor draining vessels, and there were few network vessels. The former, termed polypoidal CNV, was associated with the ARMS 2(A69S) gene and is thought to represent a deformation of the CNV under the retinal pigment epithelium. In contrast, the latter, termed PCV in the strict sense, was not associated with the ARMS 2 gene and was characterized by hyalinized arteriolosclerosis of choroidal vessels (Yuzawa 2012). The authors reported that the appearance of an orange–red nodule on ophthalmoscopy and dynamic (video) ICGA were not used as diagnostic criteria in their study (Ilginis et al. 2012). We would like to highlight the importance of both these features, which are among the six diagnostic criteria for PCV which was used in the EVEREST study (Lim et al. 2010; Koh et al. 2012). Dynamic video angiography allows visualization of the early filling patterns of the choroidal vessels, where abnormal branching vascular networks are most clearly seen. As the authors stated, pulsation of the polyps can also be seen with video angiography. While we agree that orange nodules may sometimes not be seen clearly on fundus photography due to factors such as media opacity, it may be possible to detect orange–red subretinal nodules on clinical examination. In a series of 80 patients seen in our practice, orange–red nodules were seen in 48% of cases, thus illustrating its usefulness as a diagnostic criteria. Spectral domain optical coherence tomography (OCT) is likely to play an increasingly important role in the diagnosis of PCV. Simultaneous scanning laser ophthalmoscope ICGA and OCT was found to be useful in the diagnosis of PCV, and it has been reported that the majority of PCV in that series represented a variant of Type 1 neovascular growth pattern (Khan et al. 2012). In summary, we congratulate the authors for investigating the prevalence of PCV in Scandinavian populations and would like to emphasize the role of ICGA and other imaging modalities in diagnosing PCV among patients presenting with clinical signs of neovascular AMD.