Microscope-Integrated Intraoperative Optical Coherence Tomography in Retinal Surgery

Imaging techniques of the posterior segment of the eye have gradually evolved and tremendously improved during the last decade. A widespread implementa-tion of optical coherence tomography (OCT) for the management and diagnosis of retinal conditions, with a concurrent advance in integrative technology, led to the integration of the OCT into the microscope for its intraoperative use. Regarding posterior segment eye surgery, some of the most common diagnoses in which microscope-integrated OCT (MIOCT) can result of great value are epiretinal membrane, macular hole (MH), proliferative diabetic retinopathy (PDR) and, less frequently, for inflammatory diseases, chorioretinal biopsies, and retinal implants. The impact on the surgical procedure and, possibly, on the postoperative outcome could relate to the definition of whether or not a membrane has been entirely peeled, the presence of residual membranes, and the option to perform a dissection without the need of vital dyes. The possibility of correct topographical location of hemorrhages, suspect lesions, or implants can also facilitate the surgical decision-making during biopsies or prosthesis implantation. Microscope-integrated OCT is a feasible and useful tool that can provide valuable information during surgery impact on decision-making, anatomic results, surgical safety and provide opportunity to individualize surgical treat-ment for each patient.


Introduction
The development of microsurgery enhanced the precision with which ophthalmic surgical procedures are currently performed. Its origins date back to 1876, when the first binocular magnifying device was invented by T. Saemisch of Bonn [1]. It was not until 1953, with the manufacture of a microscope with coaxial illumination, that the use of the surgical microscope became more widely available and adapted to ocular surgery [2][3][4]. Three years later, in 1956, the term "microsurgery" was used for the first time by H. M. Dekking of Göningen [5]. Almost two decades before the use of binocular magnifying devices, Hermann von Helmholtz invented ophthalmoscopy in 1851 and allowed us to see, for the first time, the human retina [6]. Under this rapidly evolving background, the development of pars plana vitrectomy (PPV) in 1970 revolutionized retinal surgery with less invasive procedures and better results in terms of visual acuity and patient satisfaction [7].
In addition to the operating microscope, imaging techniques of the posterior segment of the eye have tremendously improved during the last two decades. Optical coherence tomography (OCT) became readily and more widely available during the last 10 years and has become one of the most commonly ordered diagnostic tests in ophthalmology [8][9][10][11][12]. The detail on the retinal architecture provided by OCT allows to better characterize, diagnose, manage, and give prognosis of a wide range of vitreoretinal conditions.

Integration of OCT into the operating theater
Further improvements in software and imaging started a new transition of this powerful technology to the operating room. Firstly, it was used as a perioperative tool to image pediatric patients, with clear limitations for image acquisition, portability, and sterility [13,14], and then as a handheld OCT scan head: Bioptigen SDOIS/ Envisu portable system (Bioptigen, Research Triangle Park, NC) and Optovue IVue (Optovue, Fremont, CA) [15][16][17][18]. Advantages of the handheld OCT imaging are flexibility of scan head orientation and dynamic positioning of the scan during acquisition. On the other hand, disadvantages were its poor reproducibility, optimal targeting, and the surgeon learning curve [16,17,[19][20][21]. A further step forward was taken with the integration of an OCT scan head to the operating microscope, a model that allowed portability, stability, repeatability, efficiency, control from the foot pedal, and an easier learning curve for surgeons [16,17,[22][23][24]. However, a major drawback of this system was the need to stop the surgical procedure to image the retina: a lack of real-time imaging. The 2-year results of the Prospective Intraoperative and Perioperative Ophthalmic ImagiNg With Optical CoherEncE TomogRaphy (PIONEER) study published in 2014 [17] demonstrated the potential of this imaging tool in the operating theater. A total of 531 eyes were enrolled, from which 256 underwent posterior segment surgery. The three most frequent retinal procedures in this study were epiretinal membrane (ERM) peeling (35%), macular hole (MH) surgery (23%), and rhegmatogenous retinal detachment (RRD) repair (17%). Intraoperative OCT impacted on the surgeons' understanding of the anatomical configuration of the region of interest and/or on the surgical procedure in 43% of the cases of retinal membrane peeling and impacted on surgical decision-making in at least 13% of the procedures in which the surgeon wanted to evaluate the outcome after initial membrane peeling [17].
In order to enhance the intraoperative use of MIOCT, optimized features like automation, effective display systems, and better software analysis are required for the near future. The recent devices allow real-time and static capture acquisition of anterior and posterior segment images during surgery [31][32][33][34]. Nevertheless, they lack automation, and surgeon or assistant input can be necessary. The imaging scan is delivered to the surgeon in a dual manner: as an external display screen or a heads-up display within the oculars, providing versatility and facilitating its intraoperative use (Figure 1) [33]. Microscope-integrated OCT provides the surgeon with an additional tool to better evaluate the case in a real-time fashion, enhance surgical precision, and facilitate surgical decision-making.

Surgical implications
The intraoperative advantages of the MIOCT during surgery are wide. Table 1 summarizes the potential surgical implications according to different pathologies.

Vitreoretinal interface disorders
Conditions comprising vitreoretinal interface disorders (MH, vitreomacular traction (VMT), and ERM) result in one of the best scenarios for the use of MIOCT [34,35,37,39,40]. Intraoperative visualization of vitreomacular interface components and alterations can potentially contribute to surgical decision-making in membrane peeling procedures, because of the readiness to obtain real-time imaging of subclinical alterations (e.g., residual membranes, retinal elevations, microarchitectural perturbations in the distances between ellipsoid zone and retinal pigment epithelium (RPE), as well as alterations of the inner retinal surface) [15-17, 33,[39][40][41][42]. The ability to perform a membrane peeling with the MIOCT could result in a reduction of the use of vital dyes, a minimization of the risk of retinal pharmacotoxicity, and a reduction of surgical time [35,[43][44][45].

Macular hole
The dynamic nature of the internal limiting membrane (ILM) peeling has been evidenced with MIOCT [39,46]. Modifications of the retinal ultrastructure and geometry of MH during the ILM peeling have been described [17,31,42,[47][48][49]. Assessment of the border of the ILM peeling (Figure 2), residual ILM, retinal trauma (Figure 3), and anatomical closure (Figure 4) can be easily made in a real-time fashion [39,46]. A volume increase and base area increase of MH, with a concurrent decrease in the apex height, have been evidenced following ILM peeling  [39,46,47,50]. Additionally, the distance between ellipsoid zone and RPE and the lateral extension of this expansion have been documented and associated with anatomical and functional outcomes [16, 17, 41, 42, 47, 50-52].

Vitreomacular traction syndrome
The use of MIOCT for these cases poses a potentially useful role. Release of the traction can be confirmed; dynamic anatomical modifications, changes in outer retinal relations of ellipsoid zone and EPR and residual membranes, and formations of full-thickness macular or retinal holes can be identified as well [15, 17, 20, 33].

Epiretinal membrane
Outer retinal modifications have also been documented following ERM and/ or ILM peel in ERM. A decrease in subretinal reflectivity appreciated after these procedures correlates with a considerable expansion of the distance between the ellipsoid zone and the RPE [16, 17, 42, 47, 51]. These changes have been also  associated with visual and anatomical recovery rates; however, further studies are needed to confirm this correlation [51].

Retinal detachment
The surgical benefit of real-time OCT imaging in retinal detachment (RD) repair may not be straightforward. However, intraoperative anatomical features could be relevant for the prognosis of these cases [17,24,33]. Additionally, complex cases with severe vitreoproliferative retinopathy could be assisted with real-time imaging and successfully addressed (Figure 5B). It has been evidenced that nearly all eyes undergoing surgery with perfluorocarbon liquid tamponade have some degree of subretinal fluid (Figure 5A,B) [24,53]. According to the literature, foveal microarchitecture, the amount of submacular fluid, and the integrity of the ellipsoid zone following application of perfluorocarbon liquid may be of significance for the visual outcomes [17,24,33]. In cases where subretinal migration of perfluorocarbon liquid is present, correct visualization of the liquid bubbles and complete removal can be verified [53]. Detection of subclinical MH, occult membranes, or retinal breaks is possible with this technology, an advantage that modifies the surgical procedure and has an impact on the patient outcome [33].

Proliferative diabetic retinopathy
Vitreoretinal proliferation in diabetic retinopathy poses some of the most complex cases of vitreoretinal surgeries. The use of MIOCT can facilitate the correct  identification and visualization of the surgical planes to aid membrane dissection, delineate areas of retinal detachment, or topographically localize hemorrhages (e.g., subhyaloid, sub-ILM, or subretinal hemorrhages) [31, 33,54]. Cases of proliferative diabetic retinopathy with clinically significant macular edema can be optimally assessed to decide if an ILM peeling is needed (Figure 6) [55][56][57][58]. These clinical circumstances could potentially represent a scenario in which the use of MIOCT can facilitate surgery and enhance outcomes.

Pediatric retinal surgery
The age and cooperation of the pediatric patients make MIOCT a potentially useful tool to deploy in the examination under general anesthesia, in order to improve the understanding of pathologies such as retinopathy of prematurity (ROP), shaken baby syndrome, or any other vitreoretinal conditions that do not necessarily require VPP, like retinoblastoma [59][60][61][62]. Retinoschisis, preretinal structures and membranes, as well as lamellar or full-thickness retinal holes, which were not previously appreciated during an office examination, can be evidenced in ROP or shaken baby syndromes, respectively [59,62].

Other vitreoretinal conditions
Chorioretinal biopsy cases could be benefitted by the correct identification of the anatomical layers conforming the surgical plane and differentiation between normal tissue and lesion. The aid of MIOCT can impact on retinal prostheses implantation (e.g., Argus II implants for retinitis pigmentosa), providing precise information of the implant location and allowing a correct positioning [33,63,64].

Conclusion
The rapid technological evolution of our era has allowed us to consider this potentially powerful field of imaging to further improve retinal surgery. Evidence has demonstrated that MIOCT is feasible and useful in the operating theater, providing valuable information to evaluate the surgical field in real time which can alter surgical decision-making, positively impact on short-and long-term *Address all correspondence to: drjesusgzz@gmail.com outcomes, and possibly promote the development of new surgical techniques. In the near future, improvements in OCT-compatible surgical instrumentation, feedback systems, and software are warranted to achieve an integration of this technology to our operating theaters.

Conflict of interest
The authors have no commercial or economic conflict of interest to disclose.