Implantation of intracorneal ring segments based on the RETICS classification

In 2011, our research group carried out a study in which a classification of keratoconus was proposed taking into account different topographic, aberrometric, and biomechanical parameters, among others, and which were correlated with the patient's visual acuity [5]. Because it was a multicenter study in which different health facilities participated within the framework of health research network defined as “Red Temática de Investigación Cooperativa en Salud (RETICS)”. The classification was called the RETICS classification [3].

Subsequently, in 2013, a retrospective, multicenter, interventional study was carried out where 611 eyes of 357 patients with keratoconus were included, with a mean age of 35.15 ± 11.62 years and who underwent ICRS surgery [6]. ICRS indication was based on keratoconus diagnosis according to Rabinowitz topographical patterns [1]. Keratoconus diagnosis was based on corneal topography and slit-lamp observation. In all cases, preoperative findings characteristic of keratoconus was confirmed; that is, corneal topography revealing an asymmetric bow-tie pattern with or without skewed axes and at least one keratoconus sign on slit-lamp examination, such as localized stromal thinning, conical protrusion of the cornea at the apex, Fleischer ring, Vogt striae, or anterior stromal scarring. The number, thickness and arc length of the ICRS were selected according to the manufacturer nomograms. Corneal incision was placed in the steepest meridian taking into account the corneal topography. The patients were classified into five different groups taking into account the degree of spectacle corrected distance visual acuity (CDVA) in decimal scale as described in the RETICS classification: Grade I, patients with CDVA 0.90 or better; Grade II, patients with CDVA equal to or better than 0.60 and worse than 0.90; Grade III, patients with CDVA equal to or better than 0.40 and worse than 0.60; Grade IV, patients with CDVA equal to or better than 0.20 and worse than 0.40; and Grade Plus, patients with CDVA worse than 0.20. Additionally, success and failure indices were defined with the purpose of determining the efficacy of the surgical technique. Success was defined by those cases that presented the following characteristics 6 months after ICRS implantation:

Increase of one or more corrected or uncorrected lines of vision.

Decrease of two or more diopters in the spherical equivalent.

Reduction of at least one micron in high-order corneal aberrations or coma-like aberrations.

On the other hand, the failure criteria were the following:

Decreased one or more corrected or uncorrected lines of vision.

Increase of two or more diopters in the spherical equivalent.

Increase of at least one micron in high order corneal aberrations or coma-like aberrations.

The data obtained in the preoperative and postoperative visits: 24 h and at months 1, 3 and 6, were taken into account for the analysis of the results.

In relation to the results, we were able to observe that all the patients presented a significant improvement in uncorrected visual acuity at 6 months, regardless of the degree of keratoconus (P < 0.05). However, when analyzing the changes observed in CDVA, patients with the mild form of keratoconus, those classified as Grade I, presented a significant loss (P < 0.01) of CDVA 6 months after ICRS implantation. In all other patients, a significant improvement (P < 0.05) in the vision was observed after the surgical procedure (Table 1).

Table 1 Changes in corrected distance visual acuity (CDVA) from preoperative to postoperative 6 months (M) after intracorneal ring segment implantation

Additionally, in the present study, the loss of corrected lines of vision after ICRS implantation was analyzed, considering the severity of the disease based on the visual limitation of patients with keratoconus. We were able to observe that patients classified as Grade I had almost a 40% risk of losing two or more lines of corrected vision after the surgical procedure (Table 2). Likewise, it should be noted that the patients classified with the most severe form of the disease, Grades IV and Plus, were those who presented the greatest benefit in relation to the improvement in corrected visual acuity and, in consequence, those who presented fewer loss of lines of vision (Table 2).

Table 2 Percentage of patients that lost two or more lines of corrected distance visual acuity (CDVA) 6 months after intracorneal ring segment implantation

In relation to what was defined as success and failure indices, we noted that the success and failure rates of the ICRS implant are directly related to the visual limitation that patients have at the time of the surgical procedure. Thus, 85% of patients classified as Grade Plus will gain at least one corrected line of vision 6 months after ICRS implantation, while only 13.5% of patients classified as Grade I, will do so. In the same way, more than half of the patients classified as Grade I will lose at least one corrected line of vision after surgery, while only 11.1% of the patients classified as Grade Plus will present this loss (Table 3).

Table 3 Percentage of patients that gain or lost one line of corrected distance visual acuity (CDVA) 6 months after intracorneal ring segment implantation

The results of the present study clearly demonstrate that when analyzing the efficacy of the ICRS implantation and considering the degree of visual limitation that patients have before surgery, the patients with the greatest probability of success are those with the worst visual acuity at the time of the surgical procedure. Additionally, there is clear evidence of the poor results achieved in patients whose visual function is not compromised and therefore ICRS surgery should not be considered a proper indication in those keratoconus cases with good vision before surgery (patients with more than 0.9 in decimal scale). Therefore, nowadays we recommend ICRS implantation for keratoconus treatment in those patients with spectacle CDVA worse than 0.9 in decimal scale, poor patient motivation to wear contact lenses, or contact lens intolerance. Additionally, other specific considerations to avoid implantation are the ones recommended in the manufacturer nomograms, e.g., corneal pachymetry safety limit that suggest avoiding implantation of segments of 350 μm of thickness in corneas with less than 580 μm at sites where the tunnel will be dissected. It is also not recommended to implant ICRS in those keratoconic patients with severe central corneal scarring or with evidence of previous corneal hydrops.

Long-term results of ICRS implantation in keratoconus patients

ICRS implantation for the treatment of keratoconus is a surgical technique that has been used for the last 20 years approximately [11].

We analyzed the results of the ICRS surgery for keratoconus treatment after having followed up the patients for at least 5 years [20, 21].

In the first study, the authors analyzed 51 eyes of 35 patients with stable keratoconus with a mean age of 29.00 ± 8.84 years. Stability was defined as patients with no more than 1.00 D of change in the mean keratometric readings over the last 12 months [20]. The follow-up period was 5 years in all cases. We were able to observe a statistically significant improvement in both uncorrected and corrected visual acuity 6 months after ICRS implantation (P < 0.05). The improvement found 6 months after surgery in the visual variables did not undergo significant changes throughout the 5 years of follow-up (P > 0.30). There are several articles published in the literature in which the visual results of the ICRS implant in patients with keratoconus have been analyzed and most of them report an improvement in vision after surgery [22,23,24,25]. Additionally, some authors who have carried out analysis of the results after long periods of time have found stability of the surgical technique at the end of the follow-up period [22, 26,27,28].

The same behavior was observed in relation to the refractive parameters. Specifically, we found a statistically significant (P = 0.04) reduction in spherical equivalent 6 months after ICRS implantation, with no significant change (P = 0.57) observed over the subsequent 5 years. Once again, in the studies carried out and in which the implantation of segments has been evaluated after long periods of time, they have also observed stability of the refractive variables [22, 26, 27].

In relation to the topographic changes, we found a statistically significant reduction (P ≤ 0.02) both in the flattest, steepest and mean keratometry (Kmean), 6 months after surgery, without significant changes throughout the follow-up period. Regarding Kmean, we observed a statistically significant (P < 0.01) reduction of 3.24 D 6 months after ICRS implantation. Afterwards, a minimal regression in Kmean, of less than 1.00 D, was observed between 6 months and 5 years after the surgical procedure. It should be noted that the changes observed in Kmean between 6 months and 5 years were not statistically significant (P = 0.39; Fig. 1).

Fig. 1

Evolution of mean keratometric reading (mean K) in diopters (D) from the preoperative period (pre) through 5 years of follow-up. M, month; Y, year

In different studies that have analyzed the topographic changes in patients with keratoconus after ICRS implantation, they have reported an improvement in the keratometric variables immediately after surgery and that, in addition, these changes remain without significant changes after long follow-up periods [22, 23, 25,26,27].

This improvement was observed in the visual, refractive and topographic variables 6 months after ICRS implantation. The consequent stability throughout the 5 years of follow-up demonstrate that the benefits provided by the surgical procedure in keratoconus patients with no sign of progression remain stable and without significant changes after long follow-up periods. Finally, we must remember that the patients included in this study were patients in whom visual, refractive, and topographic stability had been confirmed for at least 12 months prior to ICRS implantation. Therefore, these results indicate that we can expect the changes found immediately after ICRS implantation to remain unchanged after long periods of follow-up in a population with stable keratoconus. However, what we cannot affirm is that the ICRS implantation can stop the progression of the disease, since for this it would be necessary to evaluate the surgical technique in a population with the progressive form of the disease.

Along the same line by analyzing the long-term result after ICR implantation in the treatment of keratoconus, we decided to study patients with keratoconus with signs of progression.

For this purpose, we carried out a study in which a total of 18 cases of patients with progressive keratoconus were included [21]. Patients analyzed in the current scientific investigation were between 19 and 30 years old (mean age of 25.75 ± 3.59 years) and were followed during a period of 5 years after ICRS implantation. Progression of the disease was defined when one or more of the following criteria was documented over a 6-month period:

1.

Increase in the steep or Kmean reading ≥ 0.75 D in a period of 6 consecutive months.

2.

Increase in the refractive cylinder ≥ 1.00 D in a period of 6 consecutive months.

3.

Increase the refractive sphere ≥ 1.00 D in a period of 6 consecutive months.

4.

Reduction of two or more corrected lines of vision in a period of 6 consecutive months.

To determine the progression of the cases, two preoperative visits were documented: the first, 6 months before ICRS implantation, and the second, just before the surgical procedure.

Here, we were able to observe a reduction in both vision and refractive variables (cylinder and spherical equivalent) during the 6 months prior to ICRS implantation, which confirmed the progressive nature of the cases we were analyzing. Subsequently, 6 months after surgery, an improvement in all the variables, both visual and refractive, was observed, which coincided with most of the series in which an improvement in vision and refraction was reported after ICRS implantation for the treatment of patients with keratoconus [23, 24, 26, 29, 30]. However, there was a regression or worsening of the effect during the follow-up between 6 months and 5 years. During the latest period, the refractive and visual variables returned to levels that are similar to those found during the preoperative assessment (Fig. 2).

Fig. 2

Evolution of the refractive variables, sphere (sph) cylinder (cyl) and spherical equivalent (SE) in diopters (D) during the follow-up period

Regarding the keratometric readings, we were able to observe a significant increase of 3.17 D in the Kmean values when we compared the first and preoperative visits (P < 0.01), which confirmed the progressive nature of the cases under analysis. Six months after the ICRS implant, we found a statistically significant reduction of 4.40 D in the Kmean (P < 0.01). Despite the significant reduction in the keratometry values at 6 months, there was a significant change in that effect throughout the follow-up period, where a regression of 3.36 D was observed in the Kmean between the visit at 6 months and the last evaluation at 5 years (Fig. 3).

Fig. 3

Evolution of mean keratometric reading in diopters (D) during the follow-up period

If we analyze the results of the two studies that were carried out in order to analyze ICRS implantation in keratoconus patients after 5 years of follow-up [20, 21], we must consider that the effect of the ICRS will depend on the stability or progression of the cases present at the time of the surgical procedure. On the one hand, we will have those patients in whom the stability of the disease has been documented and in whom the benefit obtained immediately after the procedure is expected to remain unaltered after long periods of follow-up. While in patients in whom there is clinical evidence of disease progression, the beneficial effect achieved after surgery may be lost over time. Nevertheless, it should be noted that the results of this study must be taken with cautious because of the retrospective nature of the study and the limited number of patients included in the cohort. Moreover, we have to consider that keratoconus is a progressive disease mainly during the first three decades of life. Even when progression of the disease was documented in the aforementioned study [21], we have to consider the possibility of natural stability in some of these cases as the mean age from the studied patients was 25.75 years old.

Limitations after ICRS implantation in patients with keratoconus

ICRS implantation is an effective surgical technique in improving vision and refraction in patients with keratoconus. Similarly, it is a safe and stable procedure after long periods of follow-up. However, it has certain limitations as can be expected in any type of surgery. We note that patients with good visual acuity are not good candidates for this procedure. Our results show that about 40% of patients with visual acuity of 0.9 in decimal scale or better will present loss of corrected lines of vision after surgery [6]. It is for this reason that from this point of view and based on our scientific publications, this surgical technique should not be considered in patients with good visual function due to the high percentage of patients who will lose vision after surgery.

On the other hand, regarding the long-term results, both our publications and that of most authors have shown that the ICRS implantation provides a long-term benefit in patients with keratoconus. Nevertheless, it is necessary to assess if the cases are stable or have signs of progression at the time of surgery. Thus, our scientific publications show that long-term stability can be expected if the cases are stable, that is, they do not show signs of progression at the time of surgery. On the other hand, if there is evidence of disease progression at the time of ICRS implantation, it is most likely that the benefit effect achieved during the first few months after the procedure will be almost completely lost after 5 years. It is for this reason that we must document the stability of keratoconus before considering treatment with ICRS. In the event that we have doubts or keratoconus is clearly progressing, surgery with ICRS would not be advisable because it has not been shown that this technique alone is capable of halting keratoconus progression.

Recently, our research group conducted an investigation to analyze the changes observed in patients with keratoconus that have overcome ICRS implantation in whom an extrusion had occurred [31]. Specifically, we wanted to analyze changes accounted in keratoconic patients that could be taken as prognostic factors of late extrusion in cases implanted with ICRS. For that aim, we conducted a multicenter study including 23 keratoconic corneas that were implanted with ICRS and these were followed during a period of at least 2 or more years. In all cases, a natural extrusion of one of the segments occurs at least 2 years after the primary procedure. In that study, the average time interval was 5 years. Topographic findings came close to baseline; the Kmean readings before the explantation surgery 48.97 ± 3.47 D and 47.60 ± 3.67 D after explantation (P = 0.374). Furthermore, a significant worsening in the refractive cylinder that was just after the implantation ‒2.54 ± 3.40 D changed to ‒3.96 ± 1.72 D just before extrusion (P < 0.05). The main factor obtained before ICRS implantation was the severity of the keratoconus grade, keratometric readings, and the visual acuities. After ICRS implantation, the most relevant components were the refractive cylinder, CDVA, and uncorrected distance visual acuity. Corneal aberrations were the main factors in the pre-explantation analysis. From the results of the aforementioned study, we concluded that ICRS can be safely extracted, with a regression of the corneal topographic variables towards to the preoperative level. One of the most important observations from this investigation is that a significant change in the refractive cylinder before the extrusion of the segments might be present before the explantation, suggesting that this parameter can be used as a prognostic factor in such cases [31].

Along the same lines and regarding limitations of ICRS, the authors published in year 2019 a pilot study evaluating a new design of an asymmetric long arc length intracorneal ring for the treatment of keratoconus [32]. The ring was named as VISUMRING (VR) and was characterized of having an arc length of 353 degrees and two asymmetric sections that can be customized in base width, length, and thickness (Fig. 4).

Fig. 4

Slit-lamp photograph showing the eye of a patient implanted with the VISUMRING

In this study, we analyzed the visual acuity, refraction and corneal higher-order aberrations of 30 eyes from 26 patients implanted with the VR that were followed with a mean period of 14.7 months. It was found that a significant improvement of both uncorrected and corrected vision was achieved after implantation of the VR. We also observed a significant reduction of more than 7.00 D in the spherical equivalent that correlates well with a significant flattening of the cornea which usually is observed after implantation of long arc length ICRS. Nevertheless, despite of the good clinical outcomes after implantation of the VR in keratoconic patients we found that 5 of the 30 cases needed to have a surgery to explant the VR during the follow-up due to severe focal corneal melting in the area of the incision. We hypothesize that performing a single incision for the purpose of implantation is a clear advantage, the long arc length of VR makes the ends of it fall in the stroma just beneath the incision site, leadings to wound healing alterations that can induce corneal melting and consequently, ring extrusion. This 17% explantation rate observed in our study could be considered a high complication rate and therefore implantation of ICRS with such designs should be avoided until new devices are developed and studies demonstrate their safety.

Future perspective

We recently carried out a scientific study in which it was possible to demonstrate that the use of artificial intelligence (AI) enhanced the indications of ICRS implantation. Specifically, an artificial neural network (ANN) was created to be used as a guide in ICRS surgery. In the aforementioned study, we aimed to analyze the clinical results of ANN that has been designed for the purpose of improving the predictability of ICRS implantation in the treatment of keratoconus. For that purpose, we compared 40 patients implanted with ICRS. In one of the groups, group A, we included 20 patients with keratoconus that were implanted with the Keraring ICRS (Mediphacos, Belo Horizonte, Brazil); in this group, the selection of the number (1 or 2), arc length, and thickness of ICRS was performed following the manufacturer’s nomograms. In the second group, group B, we included 20 keratoconic eyes that were also implanted with the Keraring ICRS but in this case the selection of the number (1 or 2), arc length, and thickness of ICRS was performed following the recommendation by the artificial neural network. This artificial neural network includes an algorithm that simulates which combinations of segments could provide the best topographic outcome and best corneal optical quality, and thus the best quality of vision, as a function of the Strehl ratio, for the patient [33]. In that study, we found that the spherical equivalent and the keratometric values decreased significantly in both groups. The corrected vision improved from 0.20 ± 0.21 logMAR preoperatively to 0.15 ± 0.20 logMAR postoperatively in the group B (P < 0.005), and from 0.26 ± 0.21 logMAR preoperatively to 0.22 ± 0.20 logMAR postoperatively in the group A (P < 0.01), with statistically significant differences between the two groups (P < 0.05), being better in the group where ICRS were selected using the ANN. We noted that those patients in which ANN was used in order to guide the procedure had better optical quality with a reduction in high-order corneal aberrations after the surgery when compared with those patients guided by the commercial nomogram [33]. AI based on neural networks is a dynamic process in which the system is fed (input) with new information, which improves the response it provides. It is for this reason that increasing the input of tools such as ANN can lead to an improvement in the predictability of the results of surgical techniques such as ICRS implantation and therefore improve the treatment of patients with keratoconus. Nowadays, AI is present in several of our daily activities, and is a technology that will impact every aspect of our society and change the paradigm of health care to our patients.