The Use of Anterior-Segment Optical-Coherence Tomography for the Assessment of the Iridocorneal Angle and Its Alterations: Update and Current Evidence

Journal of Clinical Medicine

Review The Use of Anterior-Segment Optical-Coherence Tomography for the Assessment of the Iridocorneal Angle and Its Alterations: Update and Current Evidence

Giacinto Triolo 1,* , Piero Barboni 2,3, Giacomo Savini 4, Francesco De Gaetano 1, Gaspare Monaco 1, Alessandro David 1 and Antonio Scialdone 1

1 Ophthalmic Institute, ASST Fatebenefratelli-Sacco, 20121 Milan, Italy; [email protected] (F.D.G.); [email protected] (G.M.); [email protected] (A.D.); [email protected] (A.S.) 2 San Raffaele Scientiﬁc Institute, University Vita-Salute, 20133 Milan, Italy; [email protected] 3 Studio Oculistico D’Azeglio, 40123 Bologna, Italy 4 G.B. Bietti Foundation I.R.C.C.S., 00198 Rome, Italy; [email protected] * Correspondence: [email protected]

Abstract: The introduction of anterior-segment optical-coherence tomography (AS-OCT) has led to improved assessments of the anatomy of the iridocorneal-angle and diagnoses of several mechanisms of angle closure which often result in raised intraocular pressure (IOP). Continuous advancements in AS-OCT technology and software, along with an extensive research in the ﬁeld, have resulted in a wide range of possible parameters that may be used to diagnose and follow up on patients with this spectrum of diseases. However, the clinical relevance of such variables needs to be explored thoroughly. The aim of the present review is to summarize the current evidence supporting the use of AS-OCT for the diagnosis and follow-up of several iridocorneal-angle and anterior-chamber Citation: Triolo, G.; Barboni, P.; alterations, focusing on the advantages and downsides of this technology. Savini, G.; De Gaetano, F.; Monaco, G.; David, A.; Scialdone, A. The Use Keywords: AS-OCT; glaucoma; iridocorneal angle; primary-angle closure; plateau-iris conﬁguration of Anterior-Segment Optical-Coherence Tomography for the Assessment of the Iridocorneal Angle and Its Alterations: Update 1. Introduction and Current Evidence. J. Clin. Med. 2021, 10, 231. https://doi.org/ Although gonioscopy is currently the gold standard for clinical assessments and 10.3390/jcm10020231 diagnoses of angle closure, being also characterized by the unique advantage of allowing a dynamic evaluation of the iridocorneal angle, it is an observer-dependent technique and,

Received: 2 December 2020 thus, is subject to intrinsic intra- and inter-individual variability. Furthermore, it may be Accepted: 4 January 2021 challenging and uncomfortable for the patient, as it includes physical contact between Published: 11 January 2021 the gonioscopic lens and the corneal surface. To overcome these limitations, anterior- segment optical-coherence tomography (AS-OCT) has recently emerged as an objective Publisher’s Note: MDPI stays neu- and noninvasive method to assess the anterior chamber and iridocorneal-angle anatomy. tral with regard to jurisdictional clai- However, there is no agreement with regard to which parameters extrapolated from ms in published maps and institutio- the AS-OCT scan are of clinical relevance, nor has it been established whether AS-OCT nal afﬁliations. is comparable to gonioscopy in detecting and monitoring iris and iridocorneal-angle anomalies [1–3]. The aim of this review is to summarize the current evidence supporting the use of AS- OCT for the diagnosis and follow-up of several iridocorneal-angle and anterior-chamber Copyright: © 2021 by the authors. Li- alterations. censee MDPI, Basel, Switzerland. This article is an open access article 2. Methods distributed under the terms and con- ditions of the Creative Commons At- A systematic search was performed across the PubMed, Scopus, and ISI Web of Sci- tribution (CC BY) license (https:// ence databases, using the following queries and/or their combination: ‘anterior segment creativecommons.org/licenses/by/ optical coherence tomography’, ‘anterior chamber optical coherence tomography’, ‘anterior 4.0/). chamber angle’, ‘narrow angle’, ‘iridocorneal angle’, ‘primary angle closure’, ‘primary

J. Clin. Med. 2021, 10, 231. https://doi.org/10.3390/jcm10020231 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 231 2 of 11

angle closure glaucoma’, ‘plateau iris syndrome’, ‘plateau iris configuration’, ‘laser peripheral iridotomy’, ‘cataract’, ‘phacoemulsification’. All identified articles underwent initial screening based on title and abstract, which was independently performed by two authors (G.T., G.M.), in order to identify relevant articles. Additionally, the references of identified articles were manually checked to find further potential studies relevant to the present review. All studies available in the literature responding to the above search criteria were then carefully evaluated for quality in terms of clinical relevance, novelty, journal of publication, study design, and sample size, and finally, they were included in the review if both the screening authors agreed that they satisfied the aforementioned requirements. Any disagreement between the two authors performing the search was assessed by consensus, and a third author (P.B.) was consulted if necessary. Articles written in a language different from English were excluded from the review process.

3. Relevant AS-OCT Parameters Several anatomical parameters were proposed for the assessment of the anterior chamber in its entirety, the iridocorneal-angle structures, and the anatomical ﬁndings in the iris.

3.1. AS-OCT Parameters Concerning the Anterior Chamber in Its Entirety The anterior chamber depth (ACD) is defined as the maximum distance from the corneal endothelium to the anterior surface of the lens, as shown in Figure1A. In their study, Sng and colleagues reported that the two variables affecting ACD values the most were the lens vault (LV) and the posterior corneal arc length (PCAL) [4]. The LV is defined as the distance from the anterior pole of the lens to the horizontal line connecting the two scleral spurs (SSs), with the SS being defined as the point at which the curvature of the inner surface of the angle wall changes noticeably (often looking as an inward protrusion of the sclera), as shown in Figure1B[ 5]. The PCAL is defined as the arc distance of the posterior corneal border between scleral spurs [6]. It has been previously shown that ACD is inversely correlated with age and hyperopic refractive errors [7–9], and that decreasing ACD is often associated with primary-angle closure (PAC) [10]. Other AS-OCT parameters featuring the AC in its entirety are the anterior chamber width (ACW), area (ACA), and volume (ACV). ACW is defined as the horizontal line corresponding to the scleral-spur-to-scleral-spur distance, as shown in Figure2A[ 11]. The ACA is defined as the area delimited by the corneal endothelium anteriorly, and the anterior iris/lens surface posteriorly (Figure2B,C). The ACA shows inverse correlation to age, while it is directly correlated to the ACD and axial length [7–9]. It is unclear whether the ACA has any correlation with the central corneal thickness, as some studies reported inverse correlation between the two parameters [7], whereas others did not [12]. Automated algorithms incorporated into modern AS-OCT devices calculate the ACV based on the ACA acquired through multiple AS-OCT scans to give a three-dimensional measurement of the AC. J. Clin. Med. 2021, 10, x FOR PEER REVIEW 3 of 12 J. Clin. Med. 2021, 10, 231 3 of 11

Figure 1. Tomey Casia 2 AS-OCT scan (Nagoya, Japan) of a patient with a narrow angle. (A) The white, bold vertical lineFigure from the1. Tomey corneal endotheliumCasia 2 AS to-OCT the anterior scan surface(Nagoya, of the Japan) lens corresponds of a patient to the wit anteriorh a narrow chamber angle. depth (ACD),(A) The measuringwhite, bold 2.218 vertical mm in the line case from reported, the corneal as shown endothelium in the bottom left to tablethe anterior (green highlighted surface cell).of the (B lens) The corresponds white, bold verticalto the line anterior from the chamber anterior surface depth of (ACD), the lens to measuring the horizontal 2.218 scleral-spur-to-scleral-spur mm in the case reported, line corresponds as shown to the lensin the vaultbottom (LV), left measuring table 0.567(green mm highligh in the sameted patient. cell). (B) The white, bold vertical line from the anterior surface of the lens to the horizontal scleral-spur-to-scleral-spur line corresponds to the lens vault (LV), measuring 0.567 mm in the same patient.

Other AS-OCT parameters featuring the AC in its entirety are the anterior chamber width (ACW), area (ACA), and volume (ACV). ACW is defined as the horizontal line corresponding to the scleral-spur-to-scleral-spur distance, as shown in Figure 2A [11]. The ACA is defined as the area delimited by the corneal endothelium anteriorly, and the anterior iris/lens surface posteriorly (Figure 2B,C). The ACA shows inverse correlation to age, while it is directly correlated to the ACD and axial length [7–9]. It is unclear whether the ACA has any correlation with the central corneal thickness, as some studies reported inverse correlation between the two parameters [7], whereas others did not [12]. Auto- mated algorithms incorporated into modern AS-OCT devices calculate the ACV based on the ACA acquired through multiple AS-OCT scans to give a three-dimensional measurement of the AC.

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Figure 2. TomeyFigure Casia2. Tomey 2 AS-OCT Casia 2 scans AS-OCT (Nagoya, scans Japan).(Nagoya, (A )Japan). The white, (A) The bold white, horizontal bold horizontal line corresponding line corre- to the scleral- spur-to-scleral-spursponding toline the shows scleral the-spur anterior-to-scl chambereral-spur width line shows(ACW) the and anterior measures chamber 11.322 mm width in this (ACW) patient and with narrow angles. (Bmeasures) The green 11.322 area, mm delimited in this patient by the cornealwith narrow endothelium angles. (B anteriorly,) The green and area, the delimited anterior surfaceby the corneal of the iris and lens posteriorly,endothelium corresponds anteriorly, to the anterior and the chamber anterior area surface (ACA) of the and iris measures and lens 15.35 posteriorly, mm2 in corresponds the same patient to the with narrow 2 angles. (C)anterior The ACA chamber from a area patient (ACA) with and open measures angles. 15.35 mm in the same patient with narrow angles. (C) The ACA from a patient with open angles. 3.2. AS-OCT Parameters Focusing on Iridocorneal Angle Structures and Iris 3.2. AS-OCT Parameters Focusing on Iridocorneal Angle Structures and Iris The angle recess area (ARA) is deﬁned as the triangular area bordered by the anterior The angle recess area (ARA) is defined as the triangular area bordered by the anterior iris surface, corneal endothelium, and a line perpendicular to the endothelium drawn from iris surface, corneala point endothelium, anterior tothe and scleral a line spur perpendicular (for instance, to 750 the mm endothelium anterior to drawnthe SS, in which case it from a point anteriorwould to be the ARA750) scleral spur to the (for iris instance, surface, 750 as shown mm anterior in Figure to 3theA[ SS,13]. in which case it would be ARA750)The angle to the opening iris surface, distance as shown (AOD) in is Figure the perpendicular 3A [13]. distance from the iris to the The angle openingtrabecular distance meshwork, (AOD) and is the it canperpendicular be measured distance at different from the distances iris to the anterior to the SS, trabecular meshwork, and it can be measured at different distances anterior to the SS, such

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assuch 250, as 500, 250, 750 500, microns 750 microns (AOD250, (AOD250, AOD50 AOD500,0, AOD750, AOD750, respectively), respectively), as shown as shownin Figure in 3B.Figure 3B. The trabecular trabecular-iris-space-iris-space area (TISA), which again can be tested and evaluated at sev- sev- eral distances fromfrom thethe SS, SS, is is deﬁned defined as as the the trapezoidal trapezoidal area area with with the the following following boundaries: boundaries:anteriorly, anteriorly, the AOD; the AOD; posteriorly, posteri aorly, line perpendiculara line perpendicular to the planeto the ofplane the innerof the corneoscleral inner corne- walloscleral drawn wall from drawn the from scleral the spur scleral to thespur opposing to the opposing iris; superiorly, iris; superiorly, the inner the corneoscleral inner corne- wall;oscleral and wall; inferiorly, and inferiorly, the anterior the irisanterior surface iris (Figure surface3 B)(Figure [14]. 3B) [14].

Figure 3.3. ((A)) Top panel.panel. SchematicSchematic diagramdiagram ofof thethe angle-recessangle-recess areaarea atat 500500 micronsmicrons fromfrom thethe scleralscleral spurspur (ARA500,(ARA500, black area). Bottom panel. Tomey CasiaCasia 22 AS-OCTAS-OCT scan scan (Nagoya, (Nagoya, Japan) Japan) of of the the angle angle showing showingin in vivo vivoARA500 ARA500 (red (red area). area). ARA ARA is definedis defined as as the the triangular triangular area area bordered bordered by by the the anterior anterior iris iris surface, surface, corneal corneal endothelium, endothelium, and and aa lineline perpendicularperpendicular toto the endothelium drawn from a point anterior to the scleral spur to the iris surface. (B) Top panel.panel. SchematicSchematic diagramdiagram of thethe trabeculartrabecular iris-spaceiris-space area atat 500500 micronsmicrons fromfrom thethe scleralscleral spurspur (TISA500,(TISA500, black area, toptop leftleft panel)panel) andand the angle-openingangle-opening distance at 500 500 and and 750 750 microns microns from from the the scleral scleral spur spur (AOD500 (AOD500 and andAOD750, AOD750, respectively, respectively, top right top rightpanel). panel). BottomBottom panel. MS-39 AS-OCT scan (CSO, Florence, Italy) of the iridocorneal angle showing in vivo TISA and AOD. AOD is the perpen- panel. MS-39 AS-OCT scan (CSO, Florence, Italy) of the iridocorneal angle showing in vivo TISA and AOD. AOD is the dicular distance from the iris to the trabecular meshwork, which can be measured at different distances anterior to the perpendicular distance from the iris to the trabecular meshwork, which can be measured at different distances anterior scleral spur, such as 250, 500, 750 microns (AOD250, AOD500, AOD750, respectively). TISA, which again can be evaluated toat several the scleral distances spur, suchfrom as the 250, scleral 500, spur 750 microns(SS), is defined (AOD250, as the AOD500, trapezoidal AOD750, area with respectively). the following TISA, boundaries: which again anteriorly can be, evaluatedthe AOD; posteriorly, at several distances a line perpendicular from the scleral to the spur plane (SS), of is the defined inner as corneoscleral the trapezoidal wall area drawn with from the followingthe scleral boundaries: spur to the anteriorly,opposing iris; the superiorly, AOD; posteriorly, the inner a linecorneoscleral perpendicular wall; toand the inferiorly, plane of thethe inneranterior corneoscleral iris surface. wall drawn from the scleral spur to the opposing iris; superiorly, the inner corneoscleral wall; and inferiorly, the anterior iris surface. Some other parameters involve iris measurements. The iris thickness (IT) is the thickness Someof the otheriris at parametersdifferent distances involve from iris measurements.the SS (e.g., IT500, The IT750) iris thickness(Figure 4A). (IT) The is theiris areathickness is defined of the as iristhe atentire different cross- distancessectional area from of the the SSiris (e.g., from IT500,the SS IT750)to the pupil (Figure (Figure4A). The4B). The iris areairis curvature is defined is asthe the perpendicular entire cross-sectional distance from area the of theiris- irispigmented from the epithelium SS to the pupilat the (Figurepoint of4 B).greatest The iris con curvaturevexity to isa theline perpendicularbetween the most distance peripheral from the and iris-pigmented the most cen- tralepithelium points of at the the iris point-pigmented of greatest epithelium convexity [13,15] to a line, as between shown thein Figure mostperipheral 4C. and the most central points of the iris-pigmented epithelium [13,15], as shown in Figure4C.

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Figure 4.FigureTomey 4. CasiaTomey 2Casia AS-OCT 2 AS-OCT scans scans (Nagoya, (Nagoya, Japan) Japan) showingshowing iris iris thickness thickness (A), (areaA), area(B), and (B), curvature and curvature (C) from (aC ) from a patient withpatient narrow with narrow angles. angles. (A) The (A) The iris iris thickness thickness (IT) (IT) is is thethe thickness of ofthe the iris irisat different at different distances distances from the from SS. In the the SS. In the example, IT measured at 750 microns (IT750) from the scleral spur (white, bold vertical line). (B) The iris area is defined example,as IT the measured entire cross at- 750sectional microns area of (IT750) the iris, from from the the scleralSS to the spur pupil. (white, (C) The bold iris curvature vertical line).is the (perpendicularB) The iris area distance is deﬁned as the entirefrom cross-sectional the iris-pigmented area ofepithelium the iris, at from the point the SS of togreatest the pupil. convexity (C) to The a line iris between curvature the most is the peripheral perpendicular and the distancemost from the iris-pigmentedcentral points epithelium of the iris-pigmented at the point epithelium of greatest (white, convexity bold vertical to a line). line between the most peripheral and the most central points of the iris-pigmented epithelium (white, bold vertical line).

3.3. Comparison between AS-OCT and Gonioscopy Nowadays, gonioscopy is still considered the gold-standard test to evaluate the iridocorneal angle. This is due to the fact that it is currently the only test allowing direct anatomical visualization of the angle, including some of its pathological ﬁndings (such as peripheral anterior synechiae, signs of appositional angle closure, and pigment dispersion) and the fact that a dynamic test can be performed as well. Therefore, the role of AS-OCT in evaluating iridocorneal angles would be to support and complete gonioscopy, rather than J. Clin. Med. 2021, 10, 231 7 of 11

replacing it. However, a direct comparison between gonioscopy and AS-OCT led, in the past, to contrasting results. Initially, Lavanya and colleagues reported a low diagnostic performance of AS-OCT in patients with gonioscopic diagnoses of narrow angles, especially in terms of specificity (with the area under the receiver-operating-characteristic curve being 0.76, sensitivity 88.4%, specificity 62.9%) [3]. Conversely, with the advent of more advanced AS-OCT software, many authors found a relatively good comparison between AS-OCT findings and gonioscopy. Nongipur et al. were among the first to report that the ACW was significantly reduced in patients with gonioscopically-defined narrow angles, compared to subjects with open angles, and in patients with gonioscopic diagnoses of primary-angle closure, compared to patients with narrow angles only [1]. More recently, the same group reported a decreased ACW, ACA, and ACV, an increased LV, and thicker irises in patients with the gonioscopic diagnosis angle closure [2]. Similarly, Wang et al. found that greater iris curvature, area, and thickness, were independently associated with narrow angles defined by gonioscopy [16].

4. Clinical Applications of AS-OCT 4.1. AS-OCT-Based Diagnosis of Primary-Angle Closure A smaller ACW, ACA, and ACV, greater iris thickness (IT) and iris area (IArea), and increased LV have been associated with angle closure [8,12,13,15]. Nongipur et al. [2] performed gonioscopy and AS-OCT in 1368 subjects, including 295 (21.6%) who showed gonioscopic angle closure. They found that PAC patients were older, had a smaller ACW, ACA, ACV, a greater LV, and thicker irises compared to patients with open angles (p < 0.01 for all). According to these findings, they proposed a classification algorithm based on stepwise logistic regression that used a combination of these six AS-OCT parameters, obtained from a single horizontal scan, able to identify subjects with a gonioscopic PAC >95% of the time. Similarly, Winegarner et al. found that the ACD, ACV, and ACA showed a high diagnostic performance in detecting PAC-disease patients with areas under the receiver-operating-characteristic curve of 0.98, 0.97, and 0.93, respectively [10]. The results from the Chinese-American Eye Study showed that the mean intraocular pressure (IOP) increased as AS-OCT parameters, such as AOD, decreased, and that IOP and AS-OCT findings were inversely correlated in angle-closure patients but not in open-angle ones [17]. Kwon et al. [18] assessed long-term changes occurring to ACD, LV, and AOD in patients with angle closure due to different mechanisms, such as pupillary block (PB), plateau-iris configuration (PIC), thick peripheral iris roll (TPIR), and exaggerated lens vault (ELV). Their study population was followed up for 41 to 54 months, with an average follow-up length of four years. They found that the baseline ACD was shallowest in ELV, followed by PB, TPIR, and PIC, in that order. The PIC group showed significantly wider AOD than the other groups at the baseline. The ACD decreased and the LV increased over time in all groups, especially in the PIC group.

4.2. AS-OCT in Plateau-Iris Configuration In the plateau-iris configuration (PIC), the iris root points anteriorly on the ciliary body or on the ciliary body itself are displaced more anteriorly than normal, critically narrowing the anterior-chamber recess by displacing the peripheral iris forward (Figure5). PIC is often associated with temporary, appositional angle closure and subsequent raised IOP, eventually leading to glaucoma. It is important to recognize PIC, because it may require additional treatment to the laser-peripheral iridotomy (LPI) usually performed in primary-angle-closure eyes, meaning argon-laser peripheral iridoplasty (ALPI), although the efficacy of this procedure remains debated. Although the diagnosis of PIC is mainly gonioscopic, this technique can be particularly tricky in evaluating the iris root position. In these cases, AS-OCT may offer an objective, noninvasive, and easy tool with which to achieve an accurate diagnosis. While AS-OCT is certainly helpful to evaluate AC and angle details with high-image resolution, it does not allow us to identify an anteriorly- J. Clin. Med. 2021, 10, 231 8 of 11

displaced ciliary-body position due to its limited capacity of deep penetration (Figure5, left panel). Conversely, ultrasound biomicroscopy (UBM) is characterized by poor deﬁni- tion in evaluating the AC and angle-anatomical ﬁndings, but it allows good visualization of J. Clin. Med. 2021, 10, x FOR PEER REVIEWthe ciliary-body position (Figure5, right). Thus, AS-OCT and UBM provide complimentary8 of 12

information in the evaluation of patients with PIC.

Figure 5. Left panel. MS-39 AS-OCT (CSO, Florence, Italy) from a patient with plateau-iris conﬁguration (PIC). Right Figure 5. Left panel. MS-39 AS-OCT (CSO, Florence, Italy) from a patient with plateau-iris configuration (PIC). Right panel. Ultra- soundpanel. biomicroscopyUltrasound (UBM) biomicroscopy of the same (UBM) eye. While of the the same AS-OCT eye. scan While provides the AS-OCT details scan of the provides iris surface, details iris of root, the and iris surface,angle structures,iris its root,penetration and angle depth structures, does not its make penetration it possible depth to doesvisualize not make the ciliary it possible body. to C visualizeonversely, the UBM ciliary is characterized body. Conversely, by poorer UBM definitionis characterized of the iris and by angle poorer structures, deﬁnition but of theit also iris allows and angle the evaluation structures, of but the it ciliary also allows-body the position. evaluation This is of particularly the ciliary-body im- portantposition. in PIC, This as it isis particularlya condition importantassociated in with PIC, anterior as it is aciliary condition-body associated displacement, with anteriorwhich displaces ciliary-body the displacement,peripheral iris whichforward, eventuallydisplaces causing the peripheralappositional iris angle forward, closure. eventually causing appositional angle closure.

PICBased is often on AS-OCT associated findings, with temporary, Verma et al. appositional reported that angle roughly closure one-third and subsequent showed raisedincidents IOP, of eventually plateau-iris leading configuration to glaucoma. among It is a groupimportant of patients to recognize with primary-angle-PIC, because it mayclosure require glaucoma additional [19], suggesting treatment the to the importance laser-peripheral of this imaging iridotomy technique (LPI) usually to evaluate per- formedalternative in primary mechanisms-angle- toclosure pupillary eyes, meaning block in patientsargon-laser with peripheral narrow iridoplasty angles. They (ALPI), also althoughidentified the the efficacy iris thickness of this at procedure 750 microns remains from thedebated. scleral Although spur (IT750) the as diagnosis the only of variable PIC is mainlysignificantly gonioscopic, associated this with technique plateau can iris. be particularly tricky in evaluating the iris root position.Interestingly, In these cases, Crowell AS- etOCT al. may reported offer thatan objective, lens and noninvasive, pupil parameters and easy evaluated tool with on whichAS-OCT to achieve scans (such an accurate as pupil diagnosis. arc, lens While vault, AS and-OCT pupil is certainly diameter) helpful showed to evaluate the greatest AC anddiagnostic angle details power with to discriminate high-imagebetween resolution, pupillary it does not block allow and us PIC to mechanismsidentify an anteriorly [20]. - displacedAlthough ciliary a- componentbody position of puredue to pupillary its limited block capacity is often of present deep penetration in patients (Figure with PIC, 5, leftthe panel). effects ofConversely, LPI alone ultrasound are, at best, bio controversial.microscopy (UBM) Leaung is et characterized al. were among by poor the firstdefini- in tion2005 in to evaluating report a case the of AC a PAC and patientangle-anatomical not responding findings, to LPI, but although it allows their good AS-OCT visualization scans ofshowed the ciliary PIC [-21body]. On position this patient, (Figure ALPI 5, wasright performed,). Thus, AS which-OCT provedand UBM effective provide in widening compli- mentarythe iridocorneal information angles in andthe evaluati reducingon the of IOP.patients with PIC. BasedMore recently,on AS-OCT Kwon findings, J et al. Verma confirmed et al. reported that LPI that was roughly ineffective one-third in widening showed thein- cidentsiridocorneal of plateau angle-iris in this configuration group of patients among [a18 group]. Ramakrishnan of patients etwith al. primary reported-angle the effect-clo- sureof ALPI glaucoma on eyes [19] with, suggesting plateau-iris the configuration, importance of on this which imaging LPI had tec alreadyhnique to been evaluate revealed al- ternativeto be unsuccessful mechanisms [22 to]. pupillary They found block that in onpatients eyes with narrow peripheral angles. anterior They synechiae,also iden- tifiedlaser-peripheral the iris thickness iridoplasty at 750 can microns be very from effective, the scleral not only spur in (IT750) lowering as the IOP only and variable number significantlyof IOP-lowering associated medications, with plateau but also iris. in increasing AOD500, TISA500, and the scleral spurInterestingly angle. , Crowell et al. reported that lens and pupil parameters evaluated on AS- OCT scans (such as pupil arc, lens vault, and pupil diameter) showed the greatest diag- 4.3. AS-OCT Changes after Laser-Peripheral Iridotomy and Cataract Extraction nostic power to discriminate between pupillary block and PIC mechanisms [20]. AlthoughIn a prospective, a componen observational,t of pure pupillary randomized, block controlled is often present trial of in 176 patients PACS with eyes PIC, un- thedergoing effects LPI, of LPI this alone procedure are, at resulted best, controversial. in an increased Leaung AOD, et TISA, al. were ARA, among ACA, the and first ACV, in 2005but not to report in an increaseda case of a ACW, PAC patient ACD, ornot LV responding [23]. Similarly, to LPI, in although a prospective their interventionalAS-OCT scans showedcase series PIC of [21] 66.PACS On this eyes, patient, Esfandiari ALPI was et al. performed, reported thatwhich the proved AOD, ARA,effective and inTISA widen- at ing the iridocorneal angles and reducing the IOP. More recently, Kwon J et al. confirmed that LPI was ineffective in widening the iridocorneal angle in this group of patients [18]. Ramakrishnan et al. reported the effect of ALPI on eyes with plateau-iris configuration, on which LPI had already been revealed to be unsuccessful [22]. They found that on eyes with peripheral anterior synechiae, laser- peripheral iridoplasty can be very effective, not only in lowering IOP and number of IOP- lowering medications, but also in increasing AOD500, TISA500, and the scleral spur angle.

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500 mm all increased by 48% to 73% (all p < 0.001) after LPI. Conversely, the LV and iris volume did not change significantly [24]. The IMPACT Study, which is a longitudinal, prospective, double-randomized research study, showed similar findings on 39 PAC/PACS eyes [25]. Kwon et al. reported a significant AOD increase in PB and TIPR patients but not in PIC and ELV patients [18]. Moghimi et al. evaluated the effects of LPI on eyes with acute primary-angle closure (APAC) and their fellow eyes [26]. LPI resulted in angle widening with a significant increase in AOD in both eyes with APAC and fellow eyes. Central ACD and ACA significantly increased, and LV decreased, in eyes with APAC, but not in their fellow eyes. Although relatively short-term changes to AS-OCT parameters are well established after LPI, the same is not the case with long-term changes. For instance, Lee et al. noticed that the AOD, TISA, and ARA significantly increased within two weeks following LPI, but had returned to their pretreatment values at the 18-month follow-up [27]. This finding basically confirmed the previous evidence from the Zhongshan Angle-Closure Prevention Trial, evaluating long-term changes to the iridocorneal angle after LPI in primary-angle-closure suspects [28]. In this randomized, controlled trial, the angle configuration was evaluated using gonioscopy, as well as angle-opening distance at 250, 500, and 750 microns from the scleral spur (AOD250, AOD500, AOD750, respectively), trabecular iris-space area (TISA500, TISA750), and angle-recess area (ARA) measured on AS-OCT images. A significant increase in all AS-OCT parameters was reported two weeks after LPI. Nevertheless, between 2 weeks and 18 months after LPI, a significant decrease in angle width was observed in treated eyes, although this finding was not statistically significant in the first six months. In untreated eyes, the angle width consistently decreased across all follow-up visits after LPI, with a more rapid longitudinal decrease compared to treated eyes. Yan C et al. used AS-OCT to compare the effects of LPI vs. lens extraction on the anterior-chamber anatomy in PACS eyes [29]. They found that the ACD increased and the LV decreased significantly in the lens-extraction group, but not in the LPI group. The effects of lens extraction on the anatomy of the anterior chamber have already been reported. Huang G et al. showed that ACD and AOD500 increased after cataract surgery, both in patients with preoperatively narrow and open angles, and found a high correlation with IOP-lowering in the former group [30]. Similar findings were confirmed later [31,32], while Nolan et al. reported an increase in the mean AOD500 (88.2%) and TISA750 (94.4%) after cataract extraction in primary-angle-closure glaucoma eyes [33]. More recently, Lee et al. demonstrated that ARA500 and TISA500 increased significantly in healthy eyes and normal-tension glaucoma eyes, with the changes in these parameters being linearly and inversely correlated with postoperative IOP changes [34].

5. Discussion Increasing evidence supports the use of AS-OCT to evaluate the anatomical details of the anterior chamber with a speciﬁc focus on the iridocorneal angle. This tool seems particularly helpful in the clinical assessment and follow-up of patients with angle closure and other angle anomalies. On the one hand, AS-OCT makes it possible to acquire detailed images of the angle anatomy, which, with complimentary gonioscopic examination, may support clinicians in diagnosing iridocorneal-angle alterations and, therefore, eventually help them to determine whether any treatment is needed. On the other hand, AS-OCT scans may provide objective proof of the laser- or surgical-treatment outcomes, and may allow a more accurate follow-up with patients with angle abnormalities. However, the above-mentioned AS-OCT advantages are counterbalanced by some limitations, which may explain why this technology is still considered a promising and helpful tool but not the gold standard. First, AS-OCT only provides a static evaluation of the angle anatomy, whereas gonioscopy remains the only diagnostic procedure allowing its dynamic evaluation. J. Clin. Med. 2021, 10, 231 10 of 11

Second, technical limitations may affect, at least partially, the current clinical useful- ness of AS-OCT. With the future advent of more sophisticated technology, the AS-OCT may provide more precise and detailed information about the anterior-segment anatomy, and this will hopefully improve the capacity of identifying iridocorneal-angle structures and detecting related anomalies. Finally, although an increasing number of AS-OCT parameters may help us to better understand the anterior-chamber anatomy and its relationship to angle-closure disease, this may generate some confusion in evaluations of AS-OCT scans. Furthermore, it needs to be taken into account that at least some of the AS-OCT parameters may not show clinical signiﬁcance and may go out of fashion in the coming years.

Author Contributions: Conceptualization, G.T. and A.S.; methodology, G.T., and P.B.; software, G.T.; validation, G.S., F.D.G. and A.D.; formal analysis, G.T.; investigation, G.T.; resources, G.T., and G.M.; data curation, G.T.; writing—original draft preparation, G.T.; writing—review and editing, G.T., and P.B.; visualization, G.M.; supervision, A.S.; project administration, G.T.; funding acquisition, none. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Because of the review nature of the present manuscript, no original data were collected. Acknowledgments: The authors thank Costruzioni Strumenti Oftalmici (CSO) Italy for their con- tribute in providing AS-OCT scan images included in the present manuscript. The contribution of G.B. Bietti Foundation I.R.C.S.S. was supported by Fondazione Roma and Italian Ministry of Health. Conﬂicts of Interest: The authors declare no conﬂict of interest.

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