**1. Introduction**

Cataract surgery is one of the most cost-effective healthcare interventions. It affects both physical and psychological health [1,2] and it has undergone a significant modernization in the past fifty years [3]. Indeed, this procedure has been made effective and safe thanks to the introduction of minimally invasive techniques and the availability of innovative equipment.

**Citation:** Toro, M.D.; Milan, S.; Tognetto, D.; Rejdak, R.; Costagliola, C.; Zweifel, S.A.; Posarelli, C.; Figus, M.; Rejdak, M.; Avitabile, T.; et al. Intraoperative Anterior Segment Optical Coherence Tomography in the Management of Cataract Surgery: State of the Art. *J. Clin. Med.* **2022**, *11*, 3867. https://doi.org/10.3390/ jcm11133867

Academic Editor: Nobuyuki Shoji

Received: 2 April 2022 Accepted: 28 June 2022 Published: 4 July 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Recently, intraoperative optical coherence tomography (i-OCT) systems have been integrated into ocular microscopes, providing useful feedback for the surgeons of both the anterior and posterior segments of the eye [4,5].

I-OCT is a non-invasive, real-time method with high resolution that can image the finest ocular structures even through mediums with significant opacity. However, to date, the extent of the actual benefits of the application of i-OCT into common clinical practice is still debated [6].

This review aims at summarizing the current applications of anterior segmen<sup>t</sup> (AS) i-OCT in the managemen<sup>t</sup> of cataract surgery while assessing the level and quality of the studies included in the review.

#### **2. Materials and Methods**

This systematic review was conducted and reported by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [7]. The review protocol was not recorded in the study design, and no registration number is available for consultation. The methodology used for this comprehensive review consisted of a systematic search of all available articles exploring the use of AS i-OCT in patients undergoing cataract surgery. A literature search of all original articles published up to November 2021 was performed in parallel by two authors (MDT and MW) using the PubMed database.

The following terms were employed for "Cataract Extraction" (Mesh) OR "Refractive Errors" (Mesh) OR "Cataract" (Mesh) OR "Lens Implantation, Intraocular" (Mesh) OR "Anterior Eye Segment" (Mesh) AND "Tomography, Optical Coherence" (Mesh).

Furthermore, the reference lists of all identified articles were examined manually to identify any potential study not captured by the electronic searches. After the preparation of the list of all electronic data captured, two reviewers (MDT and MW) examined the titles and abstracts independently and identified relevant articles. Exclusion criteria were review studies, pilot studies, case series, case reports, photo essays, and studies written in languages other than English. Moreover, studies performed on animal eyes, cadaveric eyes, and pediatric patients were excluded as well.

The same reviewers registered and selected the captured studies according to the inclusion and exclusion criteria by examining the full text of the articles. Any disagreement was assessed by consensus, and a third reviewer (MB) was consulted when necessary. No effort was made to contact the corresponding authors for further unpublished data. All selected articles were analyzed to assess the level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines [8], and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system [9].

## **3. Results**

The results of the search strategy are summarized in Figure 1. From 6302 articles extracted from the initial research, 6302 abstracts were identified for screening and 32 of these met the inclusion/exclusion criteria for full-text review. Nineteen articles were excluded (Figure 1).

Studies' characteristics, main results, level, and grade of the available evidence about the role of AS i-OCT in cataract surgery managemen<sup>t</sup> are summarized in Table 1.

**Figure 1.** Flow diagram of the study according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [7].




*J. Clin. Med.* **2022**, *11*, 3867

**Table 1.** *Cont.*

No data synthesis was possible for the heterogeneity of available data and the design of the available studies. Thus, the current review reports a qualitative analysis, detailed issue-by-issue below narratively.

The i-OCT visualization of ocular changes occurring during cataract surgery (both standard and femtosecond-laser-assisted using LenSx Laser System -Alcon Laboratories) was described by Das et al. [10]. The i-OCT employed was the RESCANTM 700 (Carl Zeiss Meditec), which is a 3 dimensional (3D) spectral-domain OCT (SD-OCT) characterized by a wavelength of 840 nm, an axial resolution of 5.5 μm, and an A-scan depth of 2000 μm. Continuous video monitoring permitted assessment of wound morphology (length, breadth, number of planes, epithelium disruption, amount of wound gape, endothelial alignment, Descemet membrane detachment-DMD) and wound closure adequacy (corneal stroma whitening and thickening induced by hydration of the side port and the main incision was qualitatively estimated), to visualize capsulorhexis, to clearly monitor hydrodissection and hydrodelineation procedures. Interestingly in two out of three posterior polar cataracts (PCCs), the opacity could be clearly distinguished from the posterior capsule and a safe hydrodissection was performed. Moreover, they applied i-OCT to image the distention of the capsular bag during intumescent cataract surgery, to decide the exact depth of trenching, and to assess the amount of wound distortion during intraocular lens (IOL) implantation, to check the final IOL position.

Tañá-Sanz et al. studied four AS parameters obtained intraoperatively with the i-OCT integrated into the Catalys (Johnson & Johnson Vision) femtosecond laser platform, which is an AS SD-OCT characterized by a central wavelength of 820–930 nm and an axial resolution of <30 μm [11]. The parameters included in the analysis were anterior chamber depth (ACD), central corneal thickness (CCT), lens thickness (LT), and white-to-white (WTW). They compared these parameters with those acquired preoperatively with two swept-source OCT (SS-OCT) biometers (IOLMaster 700-Carl Zeiss Meditec- and Anterion-Heidelberg Engineering). Statistically significant differences were shown for all parameters, with the Catalys being associated with the greatest values of ACD (mean difference with Anterion: +0.183 ± 0.056 mm; mean difference with IOL Master 700: +0.250 ± 0.054 mm), CCT (mean difference with Anterion: +32.110 ± 9.347 μm; mean difference with IOL Master 700: +24.473 ± 10.897 μm) and LT (mean difference with Anterion: +0.026 ± 0.024 mm; mean difference with IOL Master 700: +0.088 ± 0.029 mm) and the shortest WTW (mean difference with Anterion: −0.236 ± 0.604 mm; mean difference with IOL Master 700: −0.385 ± 0.575 mm).

Waring et al. used Catalys' i-OCT to study possible correlations among ACD, LT, lens diameter (LD, the distance from the intersections of the anterior to posterior lens surfaces), and lens volume (LV, the volume of the lens calculated from the measured anterior and posterior lenticular surface curvatures that were extended to intersect in the lenticular periphery) [12]. While ACD and LT could be easily detected, LD and LV could be acquired only by i-OCT and were related to lens aging. It was found that LV had a strong positive correlation with both LT and LD; all three lens anatomy parameters demonstrated a positive correlation with age (moderate for LT and LV, weak for LD). ACD showed a moderate inverse correlation with LT, a weak positive correlation with LD, and a weak inverse correlation with LV. Biometric data obtained with IOL Master 500 (Carl Zeiss Meditec) were also included. AL had a weak correlation with LD, a weak inverse correlation with LT, and no correlation with LV. The authors provided regression equations to predict LD and LV from conventionally available parameters (AL, ACD, LT, age, average WTW, and average keratometry).

Hirnschall et al. studied if intraoperative lens capsule position after crystalline lens removal could represent a useful parameter to predict IOL position [13]. A capsular tension ring (CTR) was introduced in all patients to cause a taut and straight planar posterior capsule. They used a prototype of an AS time-domain OCT (Visante-Carl Zeiss Meditec-, characterized by a wavelength of 1310 nm and an axial resolution of 18 um) combined with an operating microscope. During surgery, four screenshots were taken: at the beginning of

surgery, after irrigation/aspiration (I/A) of cortical material and Ophthalmic Viscosurgical Device (OVD) removal, after implantation of a CTR, and at the end of surgery. Intraoperative parameters were combined with ACD values acquired preoperatively, 1 hour after surgery, and three months postoperatively with PCI meter (Carl Zeiss Meditec), IOLMaster 500, and ACMaster (Carl Zeiss Meditec). Regarding immediate postoperative ACD, the position of the anterior capsule post-CTR insertion (CTRa) was associated with the highest variable importance projection (VIP), followed by the position of the anterior lens capsule after lens removal without a CTR, whereas the posterior lens capsule was a poor predictor. Regarding 1 hour after surgery ACD, it was found that AL and CTRa were excellent predictors, preoperative ACD was good, while LT was poor. AL, CTRa, and preoperatively measured ACD turned out to be excellent predictors of three-month after surgery ACD, while LT was a poor predictor.

In their study, Kurosawa et al. reported a case of posterior capsule dehiscence induced by misdirected laser irradiation, caused by the detection of a high OCT intensity area in the anterior vitreous (misinterpreted as the posterior capsule) [14]. They consequently proposed a method to avoid this complication, called LT inspection: it stands for comparing pre-operative LT (detected with IOL Master 700 and CASIA2, TOMEY) with intraoperative LT (detected with Catalys' i-OCT) before laser irradiation and, eventually, to manually correct intraoperative data based on this comparison. A total of 546 patients underwent LT inspection: in one case, an inappropriate posterior capsule line was shown, and LT inspection avoided its break. Additionally, 474 patients were retrospectively analyzed, and it was found that four patients (including the previously mentioned case of posterior capsule dehiscence) had an inappropriate posterior capsule detection. However, the "posterior capsular safety margin" (which is a laser setting) of 500 μm avoided the complication in three out of four patients.

Palanker et al. developed a system combining a frequency-domain OCT (FD-OCT, characterized by an axial resolution of 11 mm) with a femtosecond laser system [15]. They made a comparison of laser capsulotomies and manual capsulorhexis in terms of size (measured along the x and y axes, repeated after rotation by 45◦) and shape (the circularity was measured as a ratio of the sample area to the area of a disk with a diameter corresponding to the greatest linear dimension of the sample—this ratio is equal to 1 in an ideal circle). Measurements were obtained during surgery right after the capsular disk removal (with a Seibel Rhexis ruler), on the extracted capsule (after removal, they were put between glass slides, stained with 0.5% trypan blue, and then digital light microscopy was performed), and based on the digital images obtained during slit lamp exam one week and one month after surgery. Deviation from the intended size was −282 ± 305 μm in manual capsulorhexis and 27 ± 25 μm in laser capsulotomy. Concerning circularity, they calculated a 0.77 ± 0.15 ratio for manual capsulorhexis, and a 0.95 ± 0.04 ratio for the laser ones.

Titiyal et al. applied the i-OCT integrated on RESCANTM 700 to study the correlation between morphological characteristics of clear corneal incisions (CCIs) and the incidence of intraoperative DMD, comparing conventional phacoemulsification to femtosecond laserassisted cataract surgery (FLACS) [16]. Firstly, CCIs internal slit openings were classified by a single surgeon under the operating microscope, at the beginning of surgery before the occurrence of DMD, as ragged slit (RS, irregular wavy appearance) or smooth slit (SS, SS-like uniform appearance). RS morphology was observed in 31.2% of cases of the conventional surgery group and in 13.5% of cases of the FLACS group. Then, incision sites were assessed after incision creation, after phacoemulsification, after irrigation-aspiration, after IOL insertion, and after stromal hydration: DMD was described when Descemet membrane separation from the underlying stroma was visible on i-OCT or both i-OCT and the operating microscope. Forty-three out of 129 cases experienced localized incision-site DMD; incidence was significantly higher in cases with RS morphology (87.1%) than SS morphology (16.3%). All DMDs detected by i-OCT were also detectable under the operating microscope before stromal hydration: however, only i-OCT could detect an increase in its size or its onset after stromal hydration (which represented the phase in which the higher

rate of DMD occurred-83.7% cases). Incision sites were also checked one day and thirty days after surgery using slit-lamp biomicroscopy and AS-OCT (RTVue-100; Optovue): at day 30, incision-site DMD wasn't detectable in any case.

Song et al. analyzed the location of the pupil center (PC), the limbal center (LC), and the lens center (which can be extrapolated from the location of anterior and posterior lens capsule lines) with Catalys's i-OCT in patients undergoing FLACS [17]. Angle K (consequently, the location of the visual axis-VA) was acquired preoperatively with OPD scan III (Nidek). Lens center-LC distance was 0.205 ± 0.104 mm, lens center-VA distance was 0.296 ± 0.198 mm, while lens center-PC distance was 0.147 ± 0.103 mm (the smallest one); the LC was located significantly inferiorly and temporally compared to the PC. In regards to distances from the VA, the PC had a distance of 0.283 ± 0.161 mm, the LC of 0.362 ± 0.153 mm, and the lens center of 0.296 ± 0.198 mm.

In their study, Mastropasqua et al. studied capsulorhexis features after FLACS and manual cataract surgery [18]. Enrolled patients were randomly divided into three groups: patients of the first group underwent FLACS with Lensx platform (high-definition OCT visualization system), and for the second group Lenstar (Lenstar) FLACS was applied (which is guided by an integrated 3D confocal structured imaging system), while the standard manual technique was used for the last group. Regarding capsulotomy circularity, in the first seven days after surgery it was statistically significantly better in laser groups, but no statistically significant differences were observed at 30 days and 180 days. At all time points, the manual capsulorhexis area was significantly smaller than the laser one. Laser capsulotomies were also associated with a statistically significantly lower deviation from the intended size. In regards to the distance between the pupil centroid and IOL centroid, it was statistically significantly lower in laser groups than in the manual group; the distance between the pupil centroid and capsulotomy was also statistically significantly lower in laser groups than in the manual group.

Titiyal et al. analyzed morphological features and intraoperative behavior of white cataracts with RESCANTM 700 i-OCT [19]. Regarding surgical steps, capsulorhexis was done under a cohesive OVD (starting with a 26-gauge bent needle cystotome and ending using a micro forceps or needle cystotome based on the intraoperative characteristics). Bimanual I/A of cortical material was needed if an impending risk of capsulorhexis escape was detected. Difficulties in capsulorhexis were subjectively assessed by the operating surgeon based on the surgeon's control over the size and circularity of the rhexis while performing the anterior capsular flap tear. After gentle hydrodissection, nuclear emulsification and eventually I/A were performed, ending with IOL implantation. Four kinds of cataracts were described: type I (characterized by regularly organized cortical fibers), type II (with a more convex anterior capsule and multiple intralenticular clefts), type III (in which the convexity of the anterior capsule and the clefts were combined with areas of homogeneous ground glass appearance), and type IV (in which the anterior lens cortex had a homogeneous ground-glass appearance). Type I underwent uncomplicated capsulorhexis; in type II cataracts, i-OCT showed a cortical bulge in the anterior chamber during initial nick creation, standing for raised intralenticular pressure with a high risk of rhexis extension and leading the surgeon to perform a bimanual I/A till its lowering; regarding type III and type IV, the lowering of intralenticular pressure was observed at the beginning of the rhexis, outlining an increased risk of extension.

Titiyal et al. also analyzed morphological features of PPCs during standard phacoemulsification by using RESCANTM 700 i-OCT [20]. At the beginning of surgery, i-OCT was used to assess the morphology of PPC (observed as a hyperreflective region in the posterior pole area), the relation of the opacity to the posterior capsule (which appears as a continuous hyperechoic concave line limiting the posterior aspect of the nucleus) and integrity and continuity of the posterior capsule. After hydrodelineation, the relation between posterior capsule and epinuclear cushion was valued to notice any posterior capsule-epinucleus fluid interface causing accidental hydrodissection. Three types of PPCs were consequently described: type I was characterized by an intact posterior capsule visu-

alized along the entirety of the posterior polar opacity, with rly d from the capsule; in type II, the dense central region of PPC was apparently adherent to the posterior capsule, which could be detected only in the periphery; in type III the posterior capsule status couldn't be analyzed at all. The preoperative AS-OCT features correlated with the i-OCT features. Type I underwent gentle hydrodissection in addition to hydrodelineation and intraoperative posterior capsule break never occurred; type II and III underwent just hydrodelineation. Accidental hydrodissection occurred in 1 PPC type II during hydrodelineation; however, the posterior capsule remained intact till the end of surgery. Moreover, the incidence of capsule dehiscence in these i-OCT-guided surgeries (7.5%) was also retrospectively compared to not i-OCT-guided surgeries (11.1%) and statistically significant differences were noted.

Anisimova et al. studied the Berger space during and after 15 FLACS and 13 standard phacoemulsifications [6]. Videos were recorded immediately after IOL implantation (through the application of i-OCT integrated on RESCAN TM) and in the early postoperative period (with the RTVue XR 100, Optovue). Berger space was detected in 75% of cases intraoperatively and in 82% of cases postoperatively; in 32% of cases postoperatively, it was occupied by hyperreflective spots and particles, while i-OCT turned out to be more sensitive (57% of cases).

Juergens et al. described the potential benefits of i-OCT during 29 surgical procedures, among which four were cataract surgeries [21]. They employed EnFocus Ultra-Deep OCT (Leica Microsystems) integrated into the microscope, characterized by a maximum penetration depth of 11 mm, a maximum axial resolution of 9 μm, and a maximum lateral resolution of 15–31 μm. The authors described the case of a patient requiring additional implantation of a two-part, brown iris diaphragm because of post-neuro-borreliosis maximum pupillary rigidity, stating that only i-OCT imaging could assess iris diaphragm position in the capsule sac because of the poor contrast between the anterior lens capsule margin and the brown implant.
