Adaptive Optics

ISSN 0972-0200 Recent Advances Adaptive Optics 1 1 Apoorva Ayachit , Ruchi Goel , Guruprasad Ayachit2, Smriti Nagpal1, Ashwin Mohan3, Rohit Shetty3, Divya Kishore1 Guru Nanak Eye Centre, New Delhi1 M M Joshi Eye Institute, Hubli, Karnataka, India2 Narayana Nethralaya Bangalore, Karnataka, India3 have three main elements: a mechanism for wavefront correction, typically a deformable mirror; a wavefront sensor (usually Hartmann Shack type) and a command and control algorithm (software) to integrate the two4 (Figure 1). A deformable mirror is capable of changing shapes through the use of actuators that push and pull on the mirror. In the case of the Imagine Eyes system, there are 52 actuators that push and pull on an 8 × 8 array, while the system developed by Wavefront Sciences (Advanced Medical Optics, AMO, Santa Ana, California) has 800 centroids.5 In simple words, the deformable mirror by virtue of its shape changing abilities “cleans up” the aberrations sensed by the wavefront sensor and produces a sharp image despite any defocus. Abstract Physicists and ophthalmologists, since time immemorial have aggressively tried to break new ground in trying to get a good look at the retina and its myriad pathologies. Although fundus photography, optical coherence tomography and fundus fluorescein angiography have largely been very successful in imaging the retina and give a clear understanding of pathology affecting it, researchers are continuously looking for newer tools to assess the retinal structure at a cellular level. Adaptive optics with its ability to overcome optical aberrations has been able to achieve this non- invasively. Its advantages, clinical applications and shortcomings are under scrutiny and only time will reveal its utility in a clinical setting. Keywords: retinal imaging, adaptive optics The retina is a unique end organ that can be non- invasively visualized to understand the effects of ocular or systemic diseases. Fundus camera, Optical Coherence Tomography (OCT) and Scanning Laser Ophthalmoscopy (SLO) have made it possible to observe the effect of disease on neural elements, microvasculature and photoreceptors at microscopic levels.1,2 But these modalities are limited by various aberrations that interfere with imaging at a cellular level. Adaptive optics (AO) has stormed into the arena of retinal imaging and by its ability to circumvent both lower and higher order aberrations, AO has made it possible to image individual cells in the retina.3 In 1953, Horace Babcock first proposed the use of a deformable optical element, along with a wave front sensor, to compensate for atmospheric distortions in telescopic imaging. The principle of adaptive optics has been utilized in astronomical telescopes, laser communication systems, microscopy and optical fabrication. The first adaptive optics fundus camera was developed at the University of Rochester about 20 years ago.4 Figure 1: Principle of Adaptive Optics Physics and its Application Light from the retina is received by the aberrometer which then is sensed by a deformable mirror. A corrected wavefront is thus received as a high resolution retinal image. AO by itself does not produce an image and it must be integrated with an existing imaging device like a fundus camera, SLO or Spectral Domain- OCT (although flood light illumination can be used). All adaptive optics systems Adaptive optics (AO) Retinal Imaging Systems Access this article online Quick Response Code AO fundus camera: This system has been used mainly for studying the cone mosaic, cone directionality and reflectance. (Figure 2) Apart from photoreceptors; Retinal Pigment Epithelium, White Blood Cells in the vessels, retinal vessel wall and lamina cribrosa can be visualized. Considerable image processing effort is needed including registration, montaging and quantitative analysis. Despite these setbacks, AO fundus imaging has been a major breakthrough in terms of the resolution achieved.6 Website www.djo.org.in DOI http://dx.doi.org/10.7869/djo.135 Del J Ophthalmol - Vol 26 No: 1 July-September 2015 46 E-ISSN 2454-2784 Recent Advances Figure 2: AO image showing cone mosaic Adaptive optics scanning laser ophthalmoscopy (AO-SLO) - AO integrated with an SLO produces highly magnified, high resolution images. A wide field line scanning laser ophthalmoscope is used which creates an image by detection of a flying spot raster focused on the retina in a confocal arrangement. The confocality aids in better lateral resolution. Eye tracking softwares correct for micro-movements of the eyes and enable imaging even in non- mydriatic states.7 Adaptive optics Optical coherence tomography (AO-OCT) The peculiarity in OCT is that the axial and lateral resolution is decoupled. Axial resolution is limited by the coherence properties of light. Lateral resolution is limited by focal spot size, significantly degraded by the eye’s aberrations. Thus AO can be used to compensate for the eye’s monochromatic aberrations. AO is capable of resolving individual photoreceptors in 3 dimensions. 3D visualization of nerve fibre layer, lamina cribrosa, ganglion cells, as well as RPE photoreceptor mosaic and choriocapillaris is possible using high speed scans using AO- OCT (1,20,000 scans/ second) 6 Clinical Applications Zhang et al studied the inter and intra- individual variability of cones in the macula in young adults. AOSLO was used in 40 eyes of 20 subjects ranging from 19-29 years. Cone density was assessed on a sampling grid of 2.4 mm X2.4 mm in the central macula. In their study they found that peak density is 168890±21348 cones/ mm2 (mean± SD) in right eye and 167434±26068 cones/ mm2 in the left eye. Both right and left eyes exhibited sharp density gradients. At 150 micron eccentricity, the cone density was 55% of the peak and at 1.2mm, it was 10% of the peak. They noted that the AO findings correlated well with the histology findings.8 The AURA study by Dabir et al studied the cone packing density in emmetropic patients. Cone packing densities were calculated at 2 degrees and 3 degrees from the fovea in the temporal, superior, nasal and inferior quadrants. Mean cone packing densities were highest temporally, followed by superior, nasal and inferior. Mean cone packing densities at 2 degree from the fovea was 25154.67±4777.69 and at 3 degrees was 21.366.28±4167.86. Micro-perimetry revealed that the sensitivity of cones were highest at the fovea and decreased as the distance from the fovea increased. Thus they concluded that the sensitivity correlated with cone packing density.9 Retinal dystrophies- Wolfing et al studied the cone directionality, sensitivity and density in patients of atrophic Bull’s eye lesions. A 6 degree montage was obtained with the AOSLO. They demonstrated larger cones at 1.25 degrees from the fovea and decreased cone density. There was also a 5.5- fold reduction in amplitude evidenced by multi- focal ERG. This report showed that the density and functionality have a correlation and the larger cones indicated that the cones may not be normally functioning. At the foveal centre the patient’s cone density was 31,100 cones/ sq mm (normal average- 199,200 cones/ sq mm).10 Studies suggest that diabetic retinopathy could be now considered a neurovascular disorder rather than a microvasculopathy. There has been growing evidence of photoreceptor apoptosis and neural degeneration which in turn lead to vascular drop out.11 Lombardo et al11 studied the para foveal cone density in a series of 11 patients diagnosed with type 1 diabetes and studied its correlation with the duration of diabetes, glycosylated hemoglobin level, the presence of retinopathy and the SD-OCT retinal thickness. These parameters were studied in patients of no retinopathy or mild non proliferative retinopathy. The study revealed statistically significant differences in cone densities between diabetics and control healthy subjects (p <0.001). At 230, 350 and 460 microns, the average density in the study group was 91%, 90% and 89% of the average cone density in the control group, respectively. Thus there was a subtle decline in the photoreceptor density and this study revealed structural alterations at the cellular level much before clinical DR manifested.12 CSCR (Central serous chorioretinopathy) - Ooto and collaeagues used AOSLO to examine CSCR eyes with resolved subretinal fluid. Resolved CSCR have fewer cones per square mm than control subjects. They demonstrated this in patients with 20/20 or better visual acuity as well as in those with a preserved Inner Segment/Outer Segment (IS/OS) junction as seen on SD-OCT. Those patients with gaps in IS/OS junctions had further decline in the number of photoreceptors. Thus they demonstrated the subclinical loss of photoreceptors even after a single episode of CSCR, in patients who recovered excellent visual acuity.13 Macular holes- Ooto and Hangai used AOSLO to study surgically closed macular holes and their correlation with pre- operative symptom duration and visual acuity. After standard 23 gauge 3- port vitrectomy, they observed large dark areas of photoreceptor loss, the sizes of which correlated with duration of pre- operative visual symptoms. The photoreceptor density was lower even in eyes with www.djo.org.in 47 ISSN 0972-0200 Techniques maintained IS- OS junctions. Lower cone density correlated with poorer post- operative visual acuity. The dark areas corresponded to lower foveal sensitivities and thinner inner and outer segments. Darker areas on AO were larger in eyes with pre- operative cuff of fluid. AOSLO was thus valuable even in eyes with good anatomical closure seen on SD-OCT. This study gives insight into the possible pathogenesis of macular holes, which they suggest is formed by avulsion of focal neural tissue by antero- posterior traction.14 Epiretinal membranes- the structural abnormalities underlying vision changes are not known in ERMs. Only ILM folds larger than 50 microns are detectable on SDOCT or colour fundus photographs. AOSLO has revealed microfolds 520 microns in size. A study has shown the correlation of metamorphopsia with these microfolds. Thus, AOSLO in patients of metamorphopisa with a normal looking fundus or a normal SDOCT may be able to provide evidence of structural abnormalities in the photoreceptor layer.15 The pathophysiologic significance of paravascular opacification seen by AO may be either cellular infiltration or parietal thickening. AO imaging may even identify subclinical retinal vasculitis, which is not detected by ophthalmoscopy or Fundus Fluorescein Angiography. This may contribute to the diagnosis and workup of a variety of general inflammatory diseases. AO imaging may also contribute to a better understanding of the process leading to vascular occlusion, thereby helping to identify patients at risk of severe visual loss. Therefore, AO imaging may be a useful tool for the detection, early diagnosis, and management of retinal vasculitis.16 Normal blood vessels are depicted in (Figure 3). Lamina Cribrosa- The number of pores in the lamina cribrosa has been seen to be larger and of better quality in AOSLO imaging than conventional Figure 4: AO image showing pores in the lamina cribrosa colour photography (Figure 4). Pore area has also been studied and found to be larger in glaucomatous eyes. Thus, AOSLO is a useful imaging technology for assessing laminar pore number and area. The laminar pore area may be affected by axial length and IOP.17 Conclusion Thus we see that AO has far-reaching clinical applications. However, the lengthy analyses and algorithms for image acquisition, montaging and processing and patient fixation problems are some established drawbacks of AO technology. Moreover, the cost makes it prohibitive for a clinical office setting. In spite of this, recent years have seen an explosion of data on the various applications of AO in clinical research and experimental ophthalmology. The quantitative measurement of cone density based on eccentricity from the fovea, its correlation with cone functionality based on micro-perimetry and its accurate agreement with histopathology, all the while being a non- invasive technique, makes it a formidable tool in the armamentarium of a clinical researcher. It can be used to test newer treatments and surgical methods and can be used for long term longitudinal monitoring.18 Cite This Article as: Ayachit A, Goel R, Ayachit G, Nagpal S, Mohan A, Shetty R, Kishore D. Adaptive Optics. Delhi J Ophthalmol. 2015;26:46-9. Acknowledgements: None Date of Submission: 27.05.2015 Conflict of interest: None declared Figure 3: AO image showing blood vessels Del J Ophthalmol - Vol 26 No: 1 July-September 2015 48 Date of Acceptance: 14.06.15 E-ISSN 2454-2784 Recent Advances 12. References 1. Kagemann L, Ishikawa H, Wollstein G, Gabriele M, Schuman JS. Visualization of 3-D high speed ultrahigh resolution optical coherence tomographic data identifies structures visible in 2D frames. Opt Express 2009; 17:4208-20. 2. Rudnicka AR, Burk RO, Edgar DF, Fitzke FW. Magnification characteristics of fundus imaging systems. Ophthalmology 1998; 105:2186-92. 3. Kozak I. Retinal imaging using adaptive optics technology. Saudi J Ophthalmol 2014; 28:117-22. 4. 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Am J Ophthalmol 2012 ; 154:174186.e2. Ooto S, Hangai M, Takayama K, Sakamoto A, Tsujikawa A, Oshima S, et al. High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy. Ophthalmology 2011; 118:873-81. Errera MH, Coisy S, Fardeau C, Sahel JA, Kallel S, Westcott M, et al. Retinal vasculitis imaging by adaptive optics. Ophthalmology 2014; 121:1311-2.e2. Akagi T, Hangai M, Takayama K, Nonaka A, Ooto S, Yoshimura N. In vivo imaging of lamina cribrosa pores by adaptive optics scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 2012; 53:4111-9. Kim JE, Chung M. Adaptive optics for retinal imaging: current status. Retina 2013; 33:1483-6. Corresponding author: Apoorva Ayachit MS Guru Nanak Eye Centre, Maulana Azad Medical College, Maharaja Ranjit Singh Marg,New Delhi, India Email: [email protected]