**4.1 Methods and results of the application of the developed technique of vitreous body visualization in the diagnosis of idiopathic macular holes**

This aim of this work was to study the anatomical and topographic specifics of changes in VB and VRI at different stages of idiopathic macular holes (MH).

#### **Figure 11.**

*Vitreocontrast injection (red arrow) and Kenalog-40 (black arrow) in the comparative vitreous structures contrasting. The Vitreocontrast suspension provides retrociliar (red arrow) and equatorial cisterns (red arrow) contrasting.*

*Perspective Chapter: The Vitreous Body Visualization Technique in Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.109264*

#### **Figure 12.**

*Vitreocontrast injection (red arrow) and Kenalog-40 (black arrow) in the comparative vitreous structures contrasting. The Vitreocontrast suspension provides retrociliar (red arrow) and equatorial cisterns (red arrow) contrasting.*

#### **Figure 13.**

*Vitreocontrast suspension injection (red arrows) and Kenalog-40 (black arrow) suspension in comparative vitreous structures contrasting.*

We followed up 143 patients (143 eyes), 105 females, 38 males, aged 51–78 years (mean age 64.8 ± 5.3 years). Inclusion criteria for patients were the presence of MH, transparent optical medium, the absence of diabetes mellitus and other systemic diseases and ophthalmic surgical procedures in the medical history. The study exclusion criteria for patients were high myopia and traumatic MH. All patients were divided into the following three groups according to the traditional classification of the International Vitreomacular Traction Study Group (2013) [1]:


At the same time (according to the classification), in all the cases this was a primary MH without vitreomacular traction [33, 40].

The preoperative examination of patients was performed using traditional methods (visometry, tonometry; biomicroscopy of anterior segment, vitreous body and ocular fundus; B-scan, electroretinography and spectral optical coherence tomography (OCT). All the patients had a penetrating retinal defect in the macular area and increased (due to edema) retinal thickness along the MH edge. Besides, ocular fundus photography was made by MAIA fundus microperimeter (CenterVue, Italy) combining a black and white fundus camera with an image angle of 45° in addition to the perimeter. All the stages of the surgery including IIM peeling were recorded using a digital video camera Panasonic LQ-MD800E (Panasonic Corporation, Osaka, Japan) connected to operating microscope OMS-800 OFFISS (Topcon, Japan). Before each imaging session, routine exposure adjustment and calibration were performed by adjusting the white balance of the recording system to a standardized sample (Xpo-Balance, Lastolight Ltd., Coalville, Leicestershire, United Kingdom).

The intraoperative Vitreocontrastography was performed using regional infiltrational block anesthesia with central potentiation. Three-port vitrectomy was performed using 25 Short Totalplus Vitrectomy Pak under operating microscope Topcon OFFISS OMS 800 (Japan) on surgical machine Constellation (Alcon, USA). The ports were placed 4 mm from the limbus. BSS irrigation solution (Alcon Laboratories Inc., USA) was used to maintain the vitreous cavity volume during the procedure. Sterile air was used for postoperative tamponade of the vitreous cavity. All the patients underwent standard three-port 25G closed vitrectomy, a distinctive feature of which was the use of Vitreocontrast suspension for highlighting of VB and VRI structures in order to study their topographic anatomy. At the first stage, 3 25G ports were set at a distance of 4 mm from the limbus in the planar ciliary body projection at 2.30, 4.00, and 9.30 o'clock. Staining of the vitreous structures was performed sequentially through each port in order to visualize their preservation, size, topographic anatomy of intravitreal structures, and the degree of its destruction. In order to do this, we injected 0.1 ml in all the accessible quadrants using a 30G needle and stained the VB structures with Vitreocontrast suspension. After highlighting of intravitreal structures in all the segments and the video registration of anatomical topography of the VB condition, a three-port 25 G vitrectomy was performed using standard technique. The next stage was highlighting of the vitreous cortical layers. Then intraoperative induction of PVD and the removal of vitreous cortical layers with a vitreotome needle were performed in an aspiration mode. Then Vitreocontrast suspension was reapplied on the retinal surface, its excesses were removed by passive aspiration. The VRI topographic anatomy was assessed and video-recorded. If there were the remnants of cortical layers or vitreous fibers on the retinal ILM surface, their topography, area, and configuration were assessed. There were photo recording and video recording of changes in ILM topographic anatomy—abnormal PVD. In order to assess the degree of the adhesion of cortical layers to the retinal ILM surface, attempts to remove them by 25G endovitreal forceps were made. We also assessed the possibility of the cortical layer removal separately from the ILM, the degree of the adhesion, and the link of

#### *Perspective Chapter: The Vitreous Body Visualization Technique in Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.109264*

cortical layers to the MH edges. After the maximum possible removal of the vitreous cortical layers from the retinal surface, Vitreocontrast suspension was reapplied and the VRI topography was evaluated. After the mechanical removal of all the possible vitreous fibers, the retinal ILM was stained using 25G end-gripping Constellation Grieshaber forceps and the ILM around the MH was peeled. The proposed suspension made it possible to visualize the residual fibers on the ILM surface and to remove the ILM only within this area. As soon as the suspension settled on the ILM surface, the excess agent was immediately removed by passive aspiration. After the visual inspection of the macular area, we proceeded to the formation of ILM fragments using 25G end-gripping forceps. The formation of an ILM flap was started at 2.0–2.5 mm to the superior temporal arcade from the hole edge. Using micro forceps, an ILM section was separated from the retina by a pinch at the indicated point; then, gripping the ILM tip by forceps the membrane was cut off along 2–3 hourly meridians in a motion directed along the arc of an imaginary circle with MH in the center while making sure that there was no separation of the ILM from the hole edge. Then we intercepted the ILM separated along the arc at the end point and continued cutting off the ILM. By successive intercepting of the separated ILM section edges by forceps, we performed a circular separation of the ILM around the MH without the complete detachment of the fragment. Then we used a vitreotome in a "shave" mode to trim the edges of the dissected circular fragment of the ILM that were facing the vitreous cavity. After that, the ILM flap was placed in an inverted manner without mechanical impact on the foveola area.

The results of the study indicated that in the first group of patients in 64% of the cases the vitreous cisterns were elongated in the anteroposterior direction extending toward the posterior pole. The size of the cisterns was 6.5 mm in length; 8 mm in width; in 45% of cases there was disruption of the cistern wall integrity and the exit of the contrast composition outside the stained cavities that was determined from the viewpoint of VB destruction in general (64% of cases) (**Figure 14**).

After staining of cortical layers, intraoperative PVD induction with the presence of a Weiss ring was performed. At the current stage of research, this is a confirmation of the complete separation of cortical layers from retinal ILM. However, after the application of contrast suspension on retinal ILM in all the cases, a vitreous layer was highlighted on the retinal surface in the macular area that proved to the abnormal PVD and vitreoschisis (**Figure 15**).

Topographically, this vitreous layer is located in the center of the retina (macular area) and is of medium size, with 95% of cases characterized by a low degree of adhesion to the underlying tissues, friability and possibility of mechanical separation (**Figure 16**).

Upon the repeated Vitreocontrast suspension application, the retinal ILM was visualized, but in 45% of the cases, no formed vitreous cortical layer was visualized on its surface. However, the ILM itself was visualized as a result of the adhesion of particles but as a thin "dusting" since the surface is rough. In 35% of the cases, residual vitreous fibers were visualized as separate areas, half of which could be difficult to remove mechanically.

In 45% of the cases, VB was visualized on the ILM surface in the central zone, but the layer was ultrathin. In cases when residual vitreous fibers or layers were present, we performed classical circular ILM peeling with obligatory capturing of pathologically changed ILM zones characterized by the presence of ILM areas with the tight adhesion of vitreous residues, which is a risk factor for ERM formation and proliferation.

#### **Figure 14.**

*Visualization of intravitreal structures. The cisterns are elongated up to 10–12 mm, the contrast suspension out of the cavity can be seen (marked with an arrow), small MH, Group 1 patients.*

#### **Figure 15.**

*A vitreous layer on the retina after the PVD induction. On the retinal surface in the macular area, one can see a vitreous layer (vitreoschisis) with clear borders (small MH, I group patients).*

#### **Figure 16.** *Mechanical removal of the stained vitreous layer (small МH, I group patients).*

#### *Perspective Chapter: The Vitreous Body Visualization Technique in Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.109264*

The results of the study in the second group of patients evidenced that the destruction of the VB (changes in its shape, size, and integrity) was observed in 78% of the cases and was expressed in the elongation (up to 10 mm) of equatorial and retrociliary cisterns, which in 68% of cases was accompanied by the exit of the contrast agent from the cistern cavity and its settling in the macular projection zone. After staining of cortical layers and the intraoperative PVD induction, a suspension was applied on the retinal surface, and in 100% of cases, the vitreous layer was visualized on the ILM surface only in the macular area. No adhesion of the contrast suspension particles was observed throughout the rest of the retinal surface that indicated to the abnormal PVD with a vitreoschisis zone in the macular area. The vitreous layer visualized in the central zone of the retina (macular area) was of medium size. In 60% of the cases, it was characterized by a low degree of adhesion to the underlying tissues, friability and the possibility of mechanical separation (**Figures 17–19**).

In the third group of patients, the VB destruction (changes in shape, size, and integrity) was observed in all the cases and was expressed in the elongation (up to 12 mm) of equatorial and retrociliary cisterns; in 95% of cases, it was accompanied by the exit of the contrast agent from cistern cavity and its settling in the macular projection zone (**Figure 20**).

The vitreous layer visualized in the center of the retina (macular area) is medium sized. In 15% of the cases, it was characterized by the low degree of adhesion to the underlying tissues, friability and the possibility of mechanical separation (**Figure 21a** and **b** and **22a** and **b**).

Discussing the results presented, the following four main points should be mentioned. The first one is related to the choice of the basic classification of MH. In this regard, it should be noted that the concept, according to which the leading role in IMH pathogenesis is attributed to tangential vitreomacular traction (VMT), is currently generally accepted. The essence of the concept is that the radial vitreous fibers left on the perimacular surface after PVD are reduced, which gradually leads to a roundshaped retinal tear in the macular area. This theory was proposed by J. Gass [3]. And

**Figure 17.** *Macular hole contrasted.*

**Figure 18.** *Contrasted macular hole area.*

**Figure 19.** *The macular hole area contrasted can be defined and measured.*

the classification of MH with distinguishing of 4 stages was developed on its basis. This classification is widely used at the present time. However, as far as the aim of this study is concerned, this classification has a significant disadvantage since it deals exclusively with the macular area. It does not address other elements of the disease pathogenesis (changes in the VB, vitreoretinal interface) outside the macular area [41, 42].

Currently, a new anatomical classification of MH ha has been created based on optical coherence tomography data [3, 43]. Research showed the sufficient efficiency of this classification in terms of typical OCT features at different stages of MH [6, 18, 26, 44], which in general determined the choice of this classification in the present study.

*Perspective Chapter: The Vitreous Body Visualization Technique in Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.109264*

#### **Figure 20.**

*Visualization of changed intravitreal structures. Elongation of the part of cisterns in the anteroposterior direction (red arrow), complete destruction of the part of the cisterns (green arrow) exit of the contrast agent outside the cavity (blue arrow), big MH, III group patients.*

#### **Figure 21.**

*a. OCT patient pre-operation (patient А). b. Contrasting by Vitreocontrast. Vitreous body layer visualization in macular hole zone (patient А).*

The second point determines the general aspects of MH pathogenesis from the standpoint of anatomical topographic changes in the vitreous. In this regard, it should be emphasized that the trigger for the MH development is the type of the abnormal PVD, which results in the adhesion of a vitreous cortical layer in the macular projection zone. This layer has a similar topography, area, configuration in all cases irrespective of the macular hole size. In small-diameter macular holes (as the initial stage of the pathological process), this layer has no pronounced adhesion to the underlying retinal ILM and in most cases can be removed from its surface. This fact accounts for the positive anatomical effect in small diameter MH in almost 90% of cases without performing retinal ILM peeling [12, 14, 43, 45]. Later, as the pathological proliferative process develops, the

**Figure 22.**

*a. OCT Patient B. b. Vitreous body visualisation in macular hole zone patient B.*

adhesion between the vitreous layer and the ILM increases and, apparently, the process is aggravated by the contractile abilities of the ERM in formation [46, 47]. This leads to the intensification of tangential tractions and the gradual growth of MH. This thesis was confirmed by a dense cortical layer that we discovered in the large-diameter MH group of patients. In the vast majority of cases, this layer is fixed to the retinal ILM. Thus, the leading role in the MH pathogenesis belongs to the changes in the ILM of the macular area that is the development of the vitreous layer adhesion in this region. In case of PVD, it leads to its abnormal development, and the residual vitreous cortical layer stays in the macular area on the ILM surface. As the pathological process develops, the degree of the cortical layer adhesion to the retinal ILM and the contractility and tangential traction increase, which leads to an increase in the size of the hole. It should be emphasized that in all the patients, regardless of MH size, anatomical topographic changes in the vitreous were identical and were expressed primarily in the development of destruction characterized by the elongation of equatorial and retrociliary cisterns and the exit of the contrast agent from cistern cavities and its settling in the macular projection zone. It is also important to note that the destruction of the vitreous was present in small-diameter MH, i.e., at the early stages of the disease, which may indicate that changes in the vitreous occur before the development of visible (ophthalmoscopic or OCT) or clinical manifestations. Changes in the topographic anatomy of intravitreal structures have no significant differences at different stages of idiopathic macular holes, hence do not significantly influence the progression of the pathological process. The third point is related to the results of our comparative analytical assessment of the clinical diagnostic efficiency of MH treatment according to the developed techniques of VB visualization and the traditional classification. Our analysis proved to the fundamentally higher level of anatomical and morphological diagnosis of the various stages of MH by the developed techniques of VB visualization (on the basis of the original Vitreocontrastography method). In our opinion, this is associated with the following general drawbacks in the traditional classification [3, 15, 45, 48]:


*Perspective Chapter: The Vitreous Body Visualization Technique in Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.109264*


Thus, the traditional classification of MH [1, 49] does not fully reflect the basic characteristics of the pathological process (volume, topography, degree of changes in the retinal tissue) and, most importantly, practically does not assess the changes in the VB, which can trigger this disease. The stated disadvantages are certainly related to the limitations of OCT data in terms of coverage, ability to visualize transparent structures, and dependence on technical capabilities of the equipment used. Practical application of the developed VB visualization technique (based on the original vitreocontrastography method) provided the following fundamentally new possibilities for anatomical and morphological evaluation of VRI under MH:


The fourth point defines a number of MH classificational anatomic morphological signs (CAMS) from the standpoint of the vitreoretinal surgery improvement (**Table 1**).

The data presented in **Table 1** make it possible to formulate the following main directions of MH surgical treatment improvement provided by the VB visualization technique on the basis of the original vitreocontastography method:


*Note: "−"—the sign is absent, "+"—the sign is insignificantly expressed; "++"—the sign is moderately expressed, "+++" the sign is clearly expressed.*

#### **Table 1.**

*Classification of MH anatomical morphological signs developed on the basis of the original technique of VB visualization.*

#### **Figure 23.**

*OCT data (preoperational examination), patient Z.*


*Perspective Chapter: The Vitreous Body Visualization Technique in Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.109264*

#### **Figure 24.**

*a. Vitreous layer after the PVD induction, on the retinal surface in the macular area a vitreous layer with clear borders can be seen (patient Z. b. Abnormal PVD. On the retinal surface, a vitreous layer was visualized after complete intraoperative PVD induction (patient Z.). c. Removal of the cortical layer by forceps (patient Z). d–e. Removal of the cortical layer (patient Z.).*

#### **Figure 25.**

*(a and b) Vitreous layer was fixed to the edges of the MH (patients Z.). (c and d) Highlighting of retinal ILM after the removal of the vitreous cortical layer around the MH (patient Z.).*

• in the case of large-diameter MH, it is advisable to perform maximum complete removal of the upper vitreous cortical layer keeping this layer fixed to the MH edges with subsequent staining of the underlying tissues. ILM with the vitreous layer is removed along the edge (or the area) of the stained ILM with the zone of the vitreous cortical layer adhered to it corresponding to the vitreoschisis zone (patient 3).

#### **Figure 26.**

*(a and b) Removal of retinal ILM ( patient z) (c) On ILM surface there was no vitreous layer (patient Z) (d) covering of the MH by the inverted ILM flap ( patient Z).*

#### **Figure 27.**

*The flap stayed in the normal position during working with its fragments by the vitreotome (patient Z.).*

Thus, application of the developed technique of VB visualization (based on the original vitreocontrastography method) in patients with MH provides a principally new approach to clinical and diagnostic examination that is based on the development of basic classification anatomical morphological signs (visualization of structures and cortical layers (including on retina) of VB, the degree of VB adhesion, etc.) and characterized by principal advantages in comparison with traditional classifications of MR that in general makes it possible to significantly increase the clinical efficiency of vitreoretinal surgical procedures.

The points mentioned above were illustrated by the following clinical example.

Clinical case: patient Z., 64 years old, diagnosis medium diameter MH OS, at admission MCVA – 0.1, after the surgery MCVA – 0.3. The main stages of the diagnosis and treatment are presented in **Figures 23–27**.
