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Dr.Abhishek Sheemar, S19007, Dr.Mishra Divyansh Kailashcandra, Dr.Rajesh Ramanjulu, Dr.Mahesh Shanmugam P

 

Abstract

Title –OCTAmarkers and its utilisation in evaluating anti-VEGF response in neovascular age related macular degeneration (nAMD).

Synopsis – In a retrospective analysis 50 eyes with neovascular AMD treated with antiVEGF therapy with modified “Treat & Extend”protocol were analysed with OCTA (optical coherence tomography angiography).

OCTA was used to determine initial size of choroidal neovascularization (CNV) at presentation and its vascular density. Four characteristics were studied: Size of initial CNV and its correlation to response and longevity of antiVEGF therapy, initial and final BCVA and finally the overall reduction in the size and vascular density of the CNV complex. We could also in turn study the correlation between the vascular density and activity of the CNV.

Initial size of the lesion was the only factor that could be positively correlated with the number of injections, its reduction and longevity of response to anti-VEGF therapy. The reduction in CNV size was not correlated to gain in VA in contrast to existing literature.

In conclusion OCTA is a useful tool for quantitative analysis innAMD but as a predictor of functional outcome needs further evaluation.

Keywords – CNV, OCTA, neocasular AMD

Introduction

AntiVEGF therapy is currently the mainstay treatment for managing neovascular AMD.1The course of treatment is guided by activity on SD-OCT (spectral domain OCT) which is the standard imaging modality.2-4  AntiVEGF therapy as either pro re nata5 or treat and extend regimen6 is the preferred treatment regimen in AMD. OCTA is a new non-invasive imaging modality which shows retinal and choroidal vasculature based on blood flow in that vessel.7-9 it provides actual location , size and blood flow in CNV which can be useful in modifying the treatment approach with respect to each case. The vascular density as well as morphology of CNV can also be seen on OCTA.

In our study OCTA was done in neovascular AMD patients and various parameters of CNV were compared to evaluate factors predictive of antiVEGF response and role of OCTA in guiding course of antiVEGF therapy.

Methods

Retrospective records of AMD patients were reviewed from 2016 JAN to 2018 MAYwhich revealed 50 eyes with neovascular AMD treated with AntiVEGF therapy with good quality OCTA scan.

Inclusion criteria included patients with age >50 years, male or female having treatment naïve classic or occult CNV and consent for the study.Exclusion criteria consisted of type 3 neovascularization, evidence of diabetic retinopathy or any other macular or retinal vascular disease, signs or history of central serous chorioretinopathy, and hereditary retinal dystrophy. Patients with poor quality images in OCTA were also excluded from the analysis.

Diagnosis of type 1 and type 2 CNV was based on fundus biomicroscopy, fluorescein angiography (FA), and swept source OCT ((Topcon DRI OCT TRITON PLUS) and OCTA (Topcon DRI OCT TRITON PLUS). Only eyes with baseline presence of subretinal hyper-reflective material (SHRM), intraretinal or subretinal fluid (SRF), and pigment epithelial detachment (PED) were included.

Baseline evaluation consisted of slitlamp examination, indirect ophthalmoscopy, swept source OCT (Topcon DRI OCT TRITON PLUS), OCT angiography (Topcon) and FFA (fundus fluorescein angiography) wherever done.

Study protocol

OCTA 6x6mm macular scan was done in all patients. It uses OCT-A ratio analysis (OCTARA) algorithm. OCTA Ratio Analyses (OCTARA) employed by Topcon is an intensity ratio analyses and is not based on amplitude decorrelation. It does not require splitting the spectrum and therefore preserve axial resolution, which is important as SS-OCT achieve a somewhat lower axial resolution. The SS-Topcon device has a 100KHz A scan rate using a wavelength of 1050nm.10Using a  DRI  OCT  imaging  system,  SS-OCT technology can acquire 100,000 A-scans per second in both healthy and diseased eyes. Volumetric OCT scans can be acquired over a 3 × 3 mm field of view in about 4 seconds of total OCT scan time. Each B-scan position is repeatedly scanned 4 times. The examination field can be enlarged to 6 × 6 mm.10

En-face images were generated from the inner segment-outer segment junction (IS/OS) to choriocapillaris layer by manual layer segmentation performed on the OCT instrument software (IMAGEnet 6 V.1.14.8538). All images were analyzed by the two independent readers using the outer retina to choriocapillaris (ORCC) slab. Analysis of CNV size was performed on the same slab, using free image analysis software imagenet. Analysis of OCTA segmentation images at baseline and at each follow-up visit included features such as presence/absence of a high-flow network, presence/absence of an anastomotic arcade, presence/absence of a dark halo, presence/absence of flow void and vascular density.

Results 

50 eyes of 50 patients were enrolled in the study. 28 were females and 22 males. The mean was 70.2±5.6 years. 21 patients had classic CNV and 29 patients had occult CNV. The mean followup was 9.6 months. All patients received antiVEGF injections on a modified treat and extend basis. The mean number ofantiVEGFinjections were 4.

Initial size of CNV was a determinant factor in prognosticating the outcome. It was observed that patients having CNV size <1.5mm2(group A) had a better outcome as compared to >1.5mm2(group B). The mean size of CNV in group A was 0.61mm2 which was significantly lower than group B with size 3.09mm2.The mean reduction in CNV size was 74% in group A as compared to 52% in group B which related to better response in relation to size.

In group A 86% lesions were occult and in group B 67% lesions were classic suggesting larger lesions to be more of classic type.The mean number of injections in patients in group A was 3.7 as compared to 4 injections in group B.

The BCVA was not significantly correlated to the size. In group A the mean BCVA was 0.22 logmar as compared to 0.23 in group B. there was gain of vision in group A from 0.22 at first visit to 0.20 at last visit. Though there was a significant reduction in size it was significantly correlating with the vision.

Comparatively there was no gain of BCVA in group B. both initial and final mean BCVA was better in group A.In group A the mean CMT (central macular thickness) was 412.42mm and in group B was 504.66mm. The mean reduction in CMT in group A was 23.6% which was significantly better as compared to 12.37% in group B.The mean vascular density in group A was 49.97% as compared to 40.96% in group suggesting higher vascular density in smaller lesions.

Discussion

OCTA is gradually becoming an indispensable tool in evaluating diseases associated with CNV as it shows the neovascular network without angiography. Coccsa et al showed various CNV patterns and its association with treatment11 whereas Lumbroso et al described morphological changes associated with AntiVEGF therapy12. In this tudy has evaluated neovascular AMD on OCTARA in relation to various parameters and their role in prognosticating antiVEGF therapy. In this study we found that size of CNV at first visit was a key determinant in predicting response to antiVEGF therapy in this study. CNV size <1.5mm2 can be a favourable prognostic factor in terms of number of injections and reduction in size as well as CMT. Group A required a mean of 3.7 injections a s compared 4 injections in group B. the mean reduction in CNV size in group A was 74% as compared to 52% in group B. Miere et al showed that size can be a biomarker of response to antiVegf13 but a specific size as a biomarker of response has not been shown in any other study.

In terms of BCVA group A had better VA than group B but initial size of lesion did not correlated significantly with gain in VA. In both the groups’ difference of BCVA was not statically significant. So contrary to the existing literature, even if the VA is not improving anatomical reduction in size of lesion can be there suggesting response to antiVEGF therapy.

In one patient size increased from 0.86mm2 to 1.66mm2 but BCVA improved from 0.5logmar to 0.3 logmar. So direct correlation of CNV size with BCVA cannot be established. The mean reduction in CMT was significantly higher in group A suggesting earlier regression of edema in small lesions. The mean CMT was lower in group A indicating decreased activity of CNV. Vascular density is another parameter which has not been evaluated much in relation to size and type of CNV. The mean vascular density was higher in group A suggesting compact nature of small neovascular networks. One conclusion that can be drawn is that higher vascular density may not correspond to activity of CNV as mean CMT was lower in group A.

Size of CNV can also reflect the nature of CNV. In group A 86% lesion were occult and in group B 67% lesions were classic suggesting with increase in size the chances of developing a classic CNV from occult are more.

This is the only study which has evaluated neovascular AMD on OCTARA algorithm of imaging (Topcon). To calculate exact size may not be possible on FFA as dye leakage and haemorrhage can significantly hamper the exact delineation of CNV. On the other hand projection artefacts and motion artefacts can degrade the image quality. Automated segmentation may not give the best image always so manual segmentation is a better option but it can be time consuming also. Since any eye movement hampers the quality of image so patient cooperation is an important factor while capturing imageas it takes few seconds to scan the whole area.

In conclusion this study suggests that CNV size at initial visit can be used a biomarker for response to antiVEGF therapy as well number of injections needed. As the mean followup was less than a year a longer followup will better validate the results.

References

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