FP468 : Correlation of OCT and OCT Angiography (OCTA) Changes with Axial Elongation and Visual Acuity

Dr.Ramesh Venkatesh, V14265, Dr.Ashwin Mohan, Dr.Naresh Kumar Yadav, Dr.Shivani Sinha

Introduction:

High myopia is characterised by abnormal axial elongation and thinning of the sclera. Visual impairment in myopia is often accompanied by structural changes in the eye as in glaucoma, cataract, optic nerve damage, macular degeneration and retinal detachment in severe cases. In addition, myopic eyes can have more dramatic peripheral defocus than shorter eyes, which may be due to related fundus

changes such as staphyloma.These changes adversely affectthe quality of life of individuals as well as being an economic burden on health care systems. In myopia-related retinal disorders, much attention hasbeen paid to the changes in retinal microvasculaturebecause it serves as a direct source of oxygen andnutrients for the neuroretinal layers and can ultimately lead to visual impairment. Earlier studies have found that high myopia is frequently associated with retinal vascular alterations,

such as decreased retinal vessel density or increased vessel resistance, which can be detected by color doppler imaging (CDI) or fundus photography. Recently, the development of optical coherence tomography (OCT) angiography, a novel ocular blood imaging technology without using contrast agents, has made it possible to efficiently image and quantify retinal microcirculation in multiple layers by means of the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Previous studies have shown great intra-visit repeatability and inter-visitreproducibility of OCT angiography in the optic nerve head (ONH) and macular microvascular perfusion measurements. However, studies using this technology have reported conflicting results. Wang et al. evaluated the parapapillary and parafoveal microvascular perfusion using OCT angiography and found a decreased vessel density in the parapapillary area, but not in the parafoveal area, of eyes with high myopia in comparison with emmetropic eyes. Similar results were reported by Mo et al. Moreover, they observed a decreased macular flow density in pathological myopia compared with high myopia and emmetropia.

On the contrary, Yang et al. and Li et al. showed a decreased parafoveal microvascular density in eyes with high myopia when compared to those withmild myopia and emmetropia.

As far as the authors are aware, there has been a limited number of studies on assessment of structure–vascular-function relationship in myopic eyes. The hypothesis for the current study is OCT changes and vascular changes on OCTA are responsible for the decreased vison with higher grades of myopia. Therefore, in this study, we correlate the thicknessesof different macular layers, foveal angle and of retinal microvasculature with visual acuity and varying axial lengths.

Methods:

A total of 86 Indian eyes were recruited between October 2017 and March 2018for this prospective clinical study. This study was approved by the hospital Institutional Review and was conducted in accordance with the tenets of the declaration of Helsinki. A written informed consent was obtained from each participant. All subjects were required to provide a detailed medical history and undergo a thorough ophthalmic examination including measurement of refractive status, best corrected visual acuity (BCVA), intraocular pressure (IOP) measurement using Goldmann

applanation tonometry, slit-lamp examination, axial length (AL) measurement using optical low-coherence reflectometry (Lenstar; Haag-Streit AG, Koeniz, Switzerland), retinal nerve fiber layer (RNFL) and retinal layer thicknesses were measured using OCT (RTVue-XR Avanti; Optovue, Fremont, CA, USA). Foveal angle measurement was done using the open source Image J software. Retinal microvascular findings were noted using the OCT- angiography (Avanti, Optovue).

The inclusion criteria were as follows: age between 18 and 35 years, astigmatism within ± 2.00 D, BCVA of 20/25 or better, IOP less than 21 mmHg, normal anterior chamber angles, and no optic disk abnormalities. Participants with history of ocular trauma or intraocular surgery, and any ocular or systemic disorders (such as glaucoma or diabetes mellitus) which might diminish the ocular circulation were excluded. Participants where either the OCT or OCTA was not possible to procure were excluded from the study.

Retinal imaging using OCT:

The macular total thickness and individual retinal layer thicknesses at the macula were measured with spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Macular volumetric assessments consisting of horizontal axial scans with 512 A-scans per line with scanning area 6×6 mm, 25 scan patterns centred at the fovea, were performed. The scan with higher signal and image quality was selected for statistical analysis. The automatic realtime function was employed and nine images at the same location were captured and averaged automatically by the instrument software to increase image signal-to noise ratio and improve the image quality.

All thickness measurements were made automatically by SDOCT auto segmentation software before and after surgery. In cases of automatic layer misalignment, manual alignment was possible by SD-OCT software before automatic measurements. In order to limit measurement bias, we used nasal and temporal grids of retinal areas ≤ 1,750 μm away from the fovea for calculations. OCT delineates every macular layer, and we measured the thickness of individual retinal layers, e.g., IRL, outer plexiform layer(OPL), outer nuclear layer(ONL) and photoreceptor outer segment thickness (OST). IRL is composed by the retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer(IPL), inner nuclear layer (INL) and outer plexiform layer (OPL).

Foveal angle measurement using Image J:The same scan image was saved in the .jpg/.jpeg format and then exported to image J to measure the foveal angle.

Retinal microvasculature imaging with OCTangiography wad done. With a built-in AngioVue software, the Avanti spectral domain OCT (RTVue-XR Avanti; Optovue, Fremont, CA, USA) was used for retinal vessel imaging. Specifically, the signal for kinetic retinal blood was obtained using the SSADA algorithm, an amplitude-based OCT angiography method, which provided decorrelation values for each the vessel so that we could quantitatively evaluate the retinal vasculature. In this context, microvascular density and flow areas in the superficial and deep capillary plexus in the parafoveal region were calculated.

The parafoveal region was definedas a 1.9-mm-wide annulus surrounding the fovea withan inner diameter of 0.6 mm and an outer diameter of2.5 mm. The entire en-face microvasculature wasevaluated in the 3 x 3 mm area of the parafoveal region.

The retina was automatically separated into variouslayers by the AngioVue software. It should be notedthat we used the superficial and deep layers for furtheranalysis. The superficial layer extended from 3 µm below the ILM to 15 µm below the inner plexiform layer (IPL). Superficial retinalmicrovascular density was calculated separately in four sectors (superior, inferior, temporal, andnasal) in the parafoveal area based on the earlytreatment diabetic retinopathy study (ETDRS) contour. The average density of the parafoveal areawas measured. Similarly, the avascular zone area and flow density were calculated in the deep capillary layer plexus as well.

All OCT scans were performed by one proficientexaminer who was unaware of the other ocular data ofthe participants. In addition, only OCT scans with asignal strength index ≥ 70, proper segmentation, andno evident motion artefact were included.

Statistical tests:

Data collected were analysed with SPSS 24. 0 (SPSS Inc.,Chicago, IL, USA) for Macbook.

Results:

In this prospective study, we correlated the structural changes by OCT and retinal microvascular changes by OCTA in 86 eyes of 45 patients with axial length and visual acuity. Descriptive data is mentioned in Table 1.

Analysis of results:

Using the Pearson’s correlation test, we found statistically significant positive correlation of visual acuity with eye’s spherical equivalent, ONL and OST and a negative correlation with AXL and inner retinal layer thickness. No correlation was identified with OCTA findings. On correlation of the axial length with OCT and OCTA findings, significant correlations with visual acuity, spherical equivalent, foveal angle, IRL, ONL, OST and vessel density in the superficial and deep capillary plexus.See Table 2

Discussion:

In this cross-sectional study, we looked at the effects of varying axial length and refractive error on the retinal structural and vascular changes. Increased axial elongation and scleral thinning leads to myopia. Thisstudy supports our hypothesis that with axial elongation, there are clinically significant structural changes noted at the fovea and individual retinal layer thicknesses. Higher axial length is associated with poorer visual acuity. Thus, the morphological changes noted at the fovea and retinal layer thickness changes could be associated with poorer visual acuity.

The axial elongation of the eye causes stretching of the eye in the lateral direction affecting the foveal contour and individual retinal layers. In our study, we found that with increase in the axial length, there is progressive blunting of the foveal contour with persistence of the inner retinal layers and thinning of the outer retinal layers. The thickness of the IRL increases with each mm increase in AXL with thinning of the ONL and photoreceptor outer segment layer. Flattening of the foveal bulge is noted. These findings are similar to that reported in different grades of foveal hypoplasia. Blunting of foveal contour with persistence of IRL with thinning of the outer retinal layers is also noted in patients with retinopathy of prematurity and FEVR. This may be more commonly seen with eyes with high myopia.

Gua et al reported the superficial parapapillary vessel density to be reduced with increasing AXL while no relationship was noted with superficial parafoveal vessel density. Similar findings were also reported by Mo et al. In our study, we found the vessel flow density in both the SCP and DCP to be higher with increasing axial length. We explain this finding in our study due to the persistence of inner retinal layers identified on OCT in highly myopic eyes. The superficial vascular plexus is located in NFL, GCL and IPL while the deep vascular plexus is located in INL and OPL. Thus, both the retinal vascular plexuses are present within the inner retinal layers which gets thickened with increasing AXL. Another reasonable explanation is that the retinal vessels tend to supply sufficient blood flow to satisfy the metabolic demands of the neuroretina through an intrinsic autoregulatory response which means the supply would vary with the demand. In this case, the increased retinal thickness in the parafoveal region could conceivably lead to an exaggerated need of retinal blood supply, leading to an increased parafoveal microvascular density. However, it is still difficult to illuminate whether the vascular density changes a cause or consequence of the ocular structural changes based on this cross-sectional study.FAZ area was reduced in the deep vascular plexus with higher grades of myopia though not statistically significant.

It has been reported by Mo et al that macular flow density significantly decreased in pathological myopia and was positively correlated with BCVA. This is in total contrast to what we saw in our study. Our study did not show any statistically significant relationship between the retinal microvasculature and visual acuity.  This is because the foveal photoreceptors mainly derive their nutrition and oxygenation from the choriocapillaris and choroidal circulation and not from the retinal vascular plexuses. The choroid and its vasculature get thinned in the setting of high myopia. Hence, even an increase in retinal microvasculature in the parafoveal region did not affect the VA.

In summary, we demonstrated that the mechanical stretching effect of the eyeball elongation can cause structural and vascular changes in the retina affecting the visual acuity in highly myopic eyes

References:

1. Atchison DA, Jones CE, Schmid KL et al. Eye shape in emmetropia and myopia invest. Ophthalmol Vis Sci 2004;45: 3380–3386.
2. Mitchell P, Hourihan F, Sandbach J et al. The relationship between glaucoma and myopia: the blue mountains eye study. Ophthalmology 1999; 106: 2010–2015.
3. The Eye Diseases Prevalence Research Group. The prevalence of refractive errors among adults in the United States, Western Europe, and Australia. Arch Ophthalmol 2004; 122: 495–505.
4. Saw SM, Gazzard G, Shih-Yen EC et al. Myopia and associated pathological complications. Ophthalmic PhysiolOpt 2005; 25: 381–391.
5. Lam DS, Fan DS, Chan WM et al. Prevalence and characteristics of peripheral retinal degeneration inChinese adults with high myopia: a cross-sectional prevalence survey. Optom Vis Sci 2005; 82: 235–238.
6. Shimada N, Ohno-Matsui K, Nishimuta A et al. Peripapillary changes detected by optical coherence tomography in eyes with high myopia. Ophthalmology 2007; 114: 2070–2076.
7. Zejmo M, Forminska-Kapuscik M, Pieczara E et al. Etiopathogenesis and management of highdegree myopia. Part I. Med Sci Monit 2009; 15:RA199–RA202.
8. Ohno-Matsui K, Shimada N, Yasuzumi K et al. Longterm development of significant visual field defects in highly myopic eyes. Am J Ophthalmol 2011; 152:256–265.
9. Atchison DA. Effect of defocus on visual field measurement. Ophthalmic PhysiolOpt 1987; 7: 259–265.
10. Chang L, Pan CW, Ohno-Matsui K et al. Myopia-related fundus changes in Singapore adults with high myopia. Am J Ophthalmol 2013; 155: 991–999.
11. Dimitrova G, Tamaki Y, Kato S, Nagahara M (2002) Retrobulbar circulation in myopic patients with or without myopic choroidal neovascularisation. Br J Ophthalmol 86(7):771–773
12. Benavente-Pe´rez A, Hosking SL, Logan NS, Broadway DC (2010) Ocular blood flow measurements in healthy human myopic eyes. Graefe’s Arch ClinExpOphthalmol 248(11):1587–1594
13. Shimada N, Ohno-Matsui K, Harino S, Yoshida T, Yasuzumi K, Kojima A, Kobayashi K, Futagami S, Tokoro T, MochizukiM(2004) Reduction of retinal blood flow in high myopia. Graefe’s Arch ClinExpOphthalmol 242(4):284–288
14. Azemin C, Zulfaezal M, Mohamad Daud N, Ab Hamid F, Zahari I, Sapuan AH (2014) Influence of refractive condition on retinal vasculature complexity in younger subjects. Sci World J 2014:783525
15. Lim LS, Cheung CY-l, Lin X, Mitchell P, Wong TY, Mei-Saw S (2011) Influence of refractive error and axial lengthon retinal vessel geometric characteristics. Invest Ophthalmol Vis Sci 52(2):669–678