Journal of Refractive Surgery

Original Article Supplemental Data

Corneal Allogenic Intrastromal Ring Segments (CAIRS) Combined With Corneal Cross-linking for Keratoconus

Soosan Jacob, MS, FRCS, DNB; Shaila R. Patel, DNB; Amar Agarwal, MS, FRCS, FRCO; Arvind Ramalingam, Boptom; A.I. Saijimol, BSc; John Michael Raj, MSc

Abstract

PURPOSE:

To describe a new technique for the treatment of keratoconus using corneal allogenic intrastromal ring segments (CAIRS).

METHODS:

CAIRS trephined from donor cornea using a double-bladed trephine were implanted into mid-depth femtosecond laser–dissected channels in the cornea of patients with keratoconus in the 6.5-mm optic zone, followed by accelerated corneal cross-linking (A-CXL)—either conventional or contact lens–assisted CXL (A-CACXL), depending on minimum corneal thickness.

RESULTS:

Twenty patients (24 eyes) with stage 1 to 4 keratoconus (Amsler–Krumeich grading) were included. Mean follow-up was 11.58 ± 3.6 months (range: 6 to 18 months). There was significant improvement in uncorrected (2.79 ± 2.65 lines; range: 0 to 8 lines) and corrected (1.29 ± 1.33 lines; range: 0 to 5 lines) distance visual acuity, spherical equivalent, simulated maximum keratometry, steepest keratometry, topographic astigmatism, anterior and posterior best fit spheres, and mean power in the 3- and 5-mm zones. No eye showed progression during the entire follow-up. All segments remained well positioned and no segment-induced complications were seen. No other major intraoperative or postoperative complications were observed.

CONCLUSIONS:

This pilot study indicates that CAIRS with CXL may be a simple, safe, and effective option for treating keratoconus. Further studies are recommended to determine long-term outcomes.

[J Refract Surg. 2018;34(5):296–303.]

Abstract

PURPOSE:

To describe a new technique for the treatment of keratoconus using corneal allogenic intrastromal ring segments (CAIRS).

METHODS:

CAIRS trephined from donor cornea using a double-bladed trephine were implanted into mid-depth femtosecond laser–dissected channels in the cornea of patients with keratoconus in the 6.5-mm optic zone, followed by accelerated corneal cross-linking (A-CXL)—either conventional or contact lens–assisted CXL (A-CACXL), depending on minimum corneal thickness.

RESULTS:

Twenty patients (24 eyes) with stage 1 to 4 keratoconus (Amsler–Krumeich grading) were included. Mean follow-up was 11.58 ± 3.6 months (range: 6 to 18 months). There was significant improvement in uncorrected (2.79 ± 2.65 lines; range: 0 to 8 lines) and corrected (1.29 ± 1.33 lines; range: 0 to 5 lines) distance visual acuity, spherical equivalent, simulated maximum keratometry, steepest keratometry, topographic astigmatism, anterior and posterior best fit spheres, and mean power in the 3- and 5-mm zones. No eye showed progression during the entire follow-up. All segments remained well positioned and no segment-induced complications were seen. No other major intraoperative or postoperative complications were observed.

CONCLUSIONS:

This pilot study indicates that CAIRS with CXL may be a simple, safe, and effective option for treating keratoconus. Further studies are recommended to determine long-term outcomes.

[J Refract Surg. 2018;34(5):296–303.]

Intrastromal corneal ring segments (ICRS) are small curvilinear segments made of synthetic material that are implanted deep in the corneal stroma to alter the corneal curvature.1–7 They have an arc shortening effect and act as spacer agents to effect alteration in the corneal curvature and regularization of the corneal surface.1–5 Although introduced for the treatment of myopia, they are currently used more commonly for the treatment of corneal ectatic disorders, predominantly keratoconus. However, being made of synthetic material, there have been reports of complication rates up to 30%, ranging from innocuous to sight threatening5–20 (Figure A, available in the online version of this article).

Complications of synthetic intrastromal corneal ring segments (ICRS). (A) Migration and over-riding of synthetic ICRS. (B) Stromal melt and necrosis over synthetic ICRS. (C) Infectious keratitis associated with synthetic ICRS. (D) Corneal neovascularization induced by synthetic ICRS.

Figure A.

Complications of synthetic intrastromal corneal ring segments (ICRS). (A) Migration and over-riding of synthetic ICRS. (B) Stromal melt and necrosis over synthetic ICRS. (C) Infectious keratitis associated with synthetic ICRS. (D) Corneal neovascularization induced by synthetic ICRS.

We propose a new technique that uses a principle similar to synthetic segments but with the use of allogenic segments created from donor corneal buttons (Figure 1). This technique aims to decrease the complications associated with the use of synthetic material within the patient's corneal stroma. We have termed these segments corneal allogenic intrastromal ring segments (CAIRS). This has been described by one of us (SJ).

Corneal allogenic intrastromal ring segments (CAIRS) preparation. (A) The donor epithelium is completely removed from limbus to limbus using dry sponges. (B) The corneal center is marked using the reticule of the VisuMax 500-kHz femtosecond laser platform (Carl Zeiss Meditec, Jena, Germany). (C) Specially designed double-bladed circular trephine (Jacob CAIRS trephine; Madhu Instruments, New Delhi, India). (D) After removing endothelium, the trephine is centered on the inked mark using the reticule. (E) Two concentric cuts are made on the donor corneal rim. (F) A circular corneal allogenic intrastromal ring segment is seen, which is then bisected into two.

Figure 1.

Corneal allogenic intrastromal ring segments (CAIRS) preparation. (A) The donor epithelium is completely removed from limbus to limbus using dry sponges. (B) The corneal center is marked using the reticule of the VisuMax 500-kHz femtosecond laser platform (Carl Zeiss Meditec, Jena, Germany). (C) Specially designed double-bladed circular trephine (Jacob CAIRS trephine; Madhu Instruments, New Delhi, India). (D) After removing endothelium, the trephine is centered on the inked mark using the reticule. (E) Two concentric cuts are made on the donor corneal rim. (F) A circular corneal allogenic intrastromal ring segment is seen, which is then bisected into two.

Technique

The study was approved by the institutional review board of Dr. Agarwal's Eye Hospital and Eye Research Centre and the procedure conformed to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients. Patients with keratoconus between Amsler–Krumeich stages 1 and 421 showing progression and with sufficient minimum corneal thickness to allow either accelerated conventional corneal cross-linking (A-CXL) or accelerated contact lens–assisted CXL (A-CACXL)22,23 were included. Progression in a patient with keratoconus was defined as an increase in simulated maximum keratometry or steepest keratometry values of greater than 0.75 diopters (D) in the preceding 6 months. Exclusion criteria for the purpose of this study were patients older than 35 years and those with severe allergies, autoimmune and immunodeficiency syndromes, previous viral keratitis, corneas steeper than 68.00 D, central or paracentral scarring, corneas too thin (< 320 μm minimum corneal thickness) to allow A-CACXL, and history of prior corneal/intraocular surgery. All patients underwent preoperative and postoperative slit-lamp examination, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA) assessment (reported in decimal equivalent), dilated funduscopy, rigid gas permeable contact lens trial, Orbscan IIz imaging (Bausch & Lomb, Rochester, NY), anterior segment optical coherence tomography (AS-OCT) (Visante; Carl Zeiss Meditec, Jena, Germany), and specular microscopy (Tomey EM-3000; Tomey USA, Phoenix, AZ) Postoperative evaluations were at days 1, 7, and 30 and thereafter at intervals of 3 months.

CAIRS Preparation

Non-edematous donor corneal rims with negative serology for anti-HIV-1 and anti-HIV-2, hepatitis B surface antigen, anti-hepatitis C virus, and Venereal Disease Research Laboratory were taken. The endothelial cell count was not considered while assessing donor suitability. The rim was mounted on a Barron artificial anterior chamber (Katena Products Inc., Denville, NJ) and the donor epithelium completely removed from limbus to limbus using dry sponges (Weck-Cel; Beaver-Visitec International, Waltham, MA) (Figure 1A). The corneal center was marked using the reticule of the VisuMax 500-kHz femtosecond laser platform (Carl Zeiss Meditec) (Figure 1B) and the donor cornea was then dismounted and placed upside down in a Lieberman Teflon block (Appasamy Associates, Chennai, India) to strip the donor Descemet's membrane. The central mark on the donor corneoscleral rim was then centered on the central hole of the Teflon block. A specially designed double-bladed circular trephine (Jacob CAIRS trephine; Madhu Instruments, New Delhi, India) with an inner blade (outer diameter of 6.7 mm) and an outer blade (inner diameter of 7.5 mm) and a groove width of 0.40 mm (Figure 1C) was then centered on the inked mark using the reticule (Figure 1D) and used to simultaneously create two concentric cuts on the rim (Figure 1E). The full-thickness allogenic ring segment thus obtained (Figure 1F) was then bisected into two equal halves, smeared with 0.1% riboflavin in 20% dextran T500 solution (Peschke D; Peschke Trade GmbH, Huenenberg, Switzerland) and implanted.

CAIRS Implantation

The VisuMax 500-kHz femtosecond laser platform was used to create a circular channel dissected by the femtosecond laser. The parameters used were inner diameter of 6.5 mm and outer diameter of 8 mm at 50% depth of the minimum pachymetry in the 7-mm optical zone and VisuMax laser default energy setting of 300 nJ for intracorneal ring incision treatment method. Two entry incisions into the channel were created 180° opposite each other on the topographic steep axis. In patients with CDVA of better than 20/40, the incisions were positioned at the refractive steep axis in case of a difference of greater than 15° between the refractive and topographical astigmatic axes.

Both incisions were then opened using a symmetric glide (AJL Ophthalmic S.A, Araba, Spain). An 8-0 nylon suture threaded through the positioning hole of a 0.45 SK Intacs (Addition Technology, Inc., Sunnyvale, CA) was passed through one end of a CAIRS and tied down. The Intacs was passed through the channel on one side and used to pull the CAIRS after it into the channel. The CAIRS was laid out straight before being pulled in to prevent twisting of the segment (Figure B, available in the online version of this article, and Figures 2A–2B). The Intacs was brought out through the opposite incision using a reverse Sinskey hook to engage the positioning hole at the leading end. Once the CAIRS was thus drawn into and positioned within the channel, the nylon loop was cut and removed, detaching the Intacs from the CAIRS (Figure 2C). The same procedure was repeated on the other side with the second CAIRS. The final position and extension of the CAIRS within the channel was assessed visually and adjusted if required by using a curved 25-gauge microforceps (Figures 2D–2F, Video 1, available in the online version of this article).

Intacs (Addition Technology, Inc., Sunnyvale, CA) used as an instrument to implant corneal allogenic intrastromal ring segments (CAIRS). (A) CAIRS tied to the positioning hole of the Intacs is drawn into the femtosecond laser–dissected channel behind the Intacs. (B) The Intacs is drawn out of the opposite incision, leaving the first CAIRS within the channel. (C) The same is repeated on the opposite side. (D) Both CAIRS lie within the channel.

Figure B:

Intacs (Addition Technology, Inc., Sunnyvale, CA) used as an instrument to implant corneal allogenic intrastromal ring segments (CAIRS). (A) CAIRS tied to the positioning hole of the Intacs is drawn into the femtosecond laser–dissected channel behind the Intacs. (B) The Intacs is drawn out of the opposite incision, leaving the first CAIRS within the channel. (C) The same is repeated on the opposite side. (D) Both CAIRS lie within the channel.

Corneal allogenic intrastromal ring segments (CAIRS) implantation. (A) Intacs (Addition Technology, Inc., Sunnyvale, CA) tied via the positioning hole to the CAIRS is passed through the femtosecond laser–dissected channel. (B) The CAIRS is pulled into the channel behind the Intacs. (C) Intacs is drawn out of the opposite incision, leaving the first CAIRS within the channel. (D–E) The same is repeated on the other side. (F) Both CAIRS are seen lying within the femtosecond laser–dissected channel.

Figure 2.

Corneal allogenic intrastromal ring segments (CAIRS) implantation. (A) Intacs (Addition Technology, Inc., Sunnyvale, CA) tied via the positioning hole to the CAIRS is passed through the femtosecond laser–dissected channel. (B) The CAIRS is pulled into the channel behind the Intacs. (C) Intacs is drawn out of the opposite incision, leaving the first CAIRS within the channel. (D–E) The same is repeated on the other side. (F) Both CAIRS are seen lying within the femtosecond laser–dissected channel.

CXL

Table A (available in the online version of this article) summarizes the CXL methods used. The corneal epithelium was then removed and intraoperative minimum corneal thickness was measured with an ultrasound pachymeter (Echorule Plus; Biomedix, Bangalore, India) at the thinnest zone as identified on preoperative Orbscan. If greater than 400 μm, 0.1% riboflavin in 20% dextran T500 was applied to the cornea every 3 minutes for 30 minutes followed by ACXL using 10 mW/cm2 for 9 minutes to obtain a total energy of 5.4 J/cm2 (CL-UVR Rapid; Appasamy Associates, Chennai, India). If intraoperative minimum corneal thickness was less than 400 μm, the cornea and an ultraviolet barrier-free soft contact lens (Soflens made of Hilafilcon B, −0.50 diopters sphere; Bausch & Lomb) were soaked in 0.1% riboflavin in 20% dextran T500 and minimum corneal thickness remeasured after 30 minutes. Once total functional corneal thickness (cornea + subcontact lens riboflavin film + contact lens) was confirmed to be greater than 400 μm, A-CACXL23–25 proceeded using the same settings as mentioned above. If instead it was still less than 400 μm, a few drops of distilled water was instilled on the cornea to rapidly swell the corneal stroma by the minimal amount generally required and A-CACXL proceeded.26

CXL Methods

Table A:

CXL Methods

Postoperatively, topical ofloxacin (0.5 w/v) with dexamethasone (0.1 w/v) combination eye drops (SenzmoxDX; Senses Pharmaceuticals Ltd., Bengaluru, India) was given six times a day for 2 weeks and then tapered to stop over the next 3 weeks. A therapeutic bandage contact lens (Soflens; Bausch & Lomb) was used until complete epithelial healing. Tear supplements were also given and all were advised to wear ultraviolet protective glasses for 6 months after surgery as per the standard protocol after CXL.

Statistical Methods

The data were analyzed using R software (version 3.1; R Foundation for Statistical Computing, Vienna, Austria). All continuous variables were expressed using mean ± standard deviation or median (interquartile range). Normality assumption for clinical parameters and change in clinical parameters were assessed using the Shapiro–Wilk test. The comparison between the change in clinical parameters before and after treatment was done using a paired-sample t test or Wilcoxon signed-rank test based on the normality assumption. The difference in change in clinical parameters between the treatment group was tested using an independent sample t test or Mann–Whitney U test. P values of less than .05 were considered significant.

Results

Between March 2016 and March 2017, 24 eyes of 20 patients diagnosed as having keratoconus underwent CAIRS implantation, with 4 patients undergoing bilateral implantation. Of the bilaterally implanted cases, two had both eyes at stage 3, one had both eyes at stage 4, and one had one eye at stage 1 and the other at stage 2 keratoconus. The mean follow-up time was 11.58 ± 3.6 months (range: 6 to 18 months) with 13 patients having 12 or more months of follow-up. There were a total of 5 eyes with stage 1, 5 with stage 2, 10 with stage 3, and 4 with stage 4 keratoconus using the Amsler–Krumeich scale. Eleven eyes had a steepest keratometry value of greater than 58.00 diopters (D), with the steepest being 67.40 D.

On comparing preoperative with last postoperative visit parameters, there was significant improvement in UDVA, CDVA, spherical equivalent, topographic astigmatism, maximum keratometry, steepest keratometry, anterior and posterior best fit spheres, and mean power in the 3- and 5-mm zones (Table 1). There was a mean improvement of 2.79 ± 2.65 lines (range: 0 to 8 lines) in UDVA comprising 12 eyes (50%) with three or more lines, 5 eyes (20.83%) with one and two lines, and 7 eyes (29.16%) with no improvement. CDVA improved by a mean of 1.29 ± 1.33 lines (range: 0 to 5 lines) with an improvement of three of more lines in 4 eyes (16.66%), between one and two lines in 11 eyes (45.83%), and no improvement in 9 eyes (37.5%). No eye showed a loss of UDVA or CDVA.

Comparison of Preoperative and Last Postoperative Visit Clinical Parameters (N = 24)

Table 1:

Comparison of Preoperative and Last Postoperative Visit Clinical Parameters (N = 24)

The segments were not visible on naked eye examination in any patient. All segments remained well positioned and no case of melt or corneal necrosis was encountered. No other major intraoperative or postoperative complication was seen.

The mean preoperative thinnest corneal thickness was 409 ± 65.5 μm and the mean minimum corneal thickness in the 7-mm zone was 548.3 ± 43.3 μm. The average depth of implantation was 314.4 ± 61 μm. Eighteen eyes underwent A-CACXL and 6 eyes underwent A-CXL. The subgroup analysis between these two groups did not show any significant difference in any parameter (Table B, available in the online version of this article). The depth of the demarcation line seen as a difference in reflectivity between the anterior and posterior stroma was measured at the 1-month postoperative visit using the AS-OCT. The average of 12 measurements taken at the 3-, 6-, and 8-mm zones at the 90° and 180° axes centered on the pupil was taken. No significant difference was seen in the demarcation line between the two groups (A-CACXL = 222.07 ± 32.37 μm, A-CXL = 230.22 ± 24.16 μm; mean difference: −8.15 μm; 95% CI = −38.16 to 21.86; P = .5788). AS-OCT also showed well-placed segments at midstromal depth without signs of incompatibility such as necrosis, edema, or inflammation of the segment or the surrounding host stroma.

Subgroup Analysis Between Eyes That Underwent Conventional A-CXL and A-CACXL

Table B:

Subgroup Analysis Between Eyes That Underwent Conventional A-CXL and A-CACXL

There was no significant difference in mean preoperative and postoperative minimum corneal thickness as measured by AS-OCT pachymetry. Mean preoperative and postoperative specular count was 2,850 ± 209 and 2,747 ± 235 cells/mm2, respectively. No eye showed progression as defined by an increase in maximum or steepest keratometry measured by Orbscan of greater than 0.75 D during the entire follow-up period. Light microscopy of the CAIRS showed regular, evenly cut segments and structurally unaltered normal corneal tissue (Figures CD, available in the online version of this article).

Corneal allogenic intrastromal ring segments (CAIRS) postoperatively. (A) Light microscopic image of the CAIRS showing regular, even cuts and structurally unaltered normal corneal tissue. (B) Slit-lamp photograph showing the CAIRS. (C) Time-domain anterior segment optical coherence tomography (AS-OCT) showing the CAIRS and demarcation line. (D) Spectral-domain AS-OCT showing the CAIRS.

Figure C.

Corneal allogenic intrastromal ring segments (CAIRS) postoperatively. (A) Light microscopic image of the CAIRS showing regular, even cuts and structurally unaltered normal corneal tissue. (B) Slit-lamp photograph showing the CAIRS. (C) Time-domain anterior segment optical coherence tomography (AS-OCT) showing the CAIRS and demarcation line. (D) Spectral-domain AS-OCT showing the CAIRS.

(A) Keratometric maps showing decrease in parameters from preoperatively to 2 weeks postoperatively. (B) Another patient showing improved parameters 1 month after implantation of corneal allogenic intrastromal ring segments (CAIRS). D = diopters; sim K = simulated keratometry; astig = astigmatism

Figure D.

(A) Keratometric maps showing decrease in parameters from preoperatively to 2 weeks postoperatively. (B) Another patient showing improved parameters 1 month after implantation of corneal allogenic intrastromal ring segments (CAIRS). D = diopters; sim K = simulated keratometry; astig = astigmatism

Discussion

Synthetic implants within the eye in the form of intrastromal rings have been reported to be associated with up to a 30% incidence5 of postoperative complications such as segment migration,6,7 over-riding,8 stromal thinning, corneal melt and necrosis,6,9 late dislocation into the anterior chamber,10 late intrusion into anterior chamber causing corneal hydrops,20 and exposure and extrusion of the segment. They may also be associated with the risk of infectious keratitis, which can be sight-threatening.6,11–15 Other more innocuous complications reported include corneal neovascularization,16,17 mild channel deposits, corneal haze,18 corneal melting (especially with shallow implantation or with constant eye rubbing), focal edema and other reported histopathologic changes19 around segments. Our technique uses allogenic tissue as implantable segments in patients with keratoconus to obtain a spacer effect and provide a more regularized topography similar to that of synthetic ICRS while at the same time avoiding possible complications associated with implanting synthetic material.

In our series, significant improvement was seen in UDVA, CDVA, spherical equivalent, and topographic parameters (Table 1). Unlike synthetic ICRS, CAIRS are non-rigid, soft, and pliable in nature. Despite this, flattening and regularization of the corneal topography was obtained and this can be explained by the Barraquer thickness law, which states that the outcome achieved is directly proportional to the thickness of the segment and inversely proportional to its diameter.27–29 Because segments of full-thickness corneal stroma from the 6.7- to 7.5-mm optic zone of the donor cornea are used, sufficient thickness gives a spacer effect in the patient's cornea, thus causing flattening and topographic regularization.

ICRS made of synthetic material require deep implantation at approximately 80% depth27,28 and a minimum corneal thickness of at least 450 μm in the 6- to 7-mm optic zone of implantation.30 Sufficient corneal stroma needs to be retained above the synthetic implant to prevent erosion and extrusion. Deep implantation has also been reported to be associated with complications such as Descemet detachment,31 acute hydrops,32 late dislocation into the anterior chamber,10 and superficial erosion. The use of allogenic tissue implanted at mid-stromal depth is likely to avoid these risks and may be associated with a lesser risk of movement or migration either spontaneously or with eye rubbing than hard, rigid synthetic material such as Intacs, Ferrara rings (AJL Ophthalmic, Araba, Spain), or Kerarings (Mediphacos, Inc., Belo Horizante, Brazil). Therefore, allogenic tissue may allow the possibility of being able to be implanted in a wider range of depths with less risk of complications. Longer term studies would be required to verify this. In our study, postoperative AS-OCT showed well-placed segments at midstromal depth that remained in the same position over the follow-up period. The average depth of implantation was 314.4 ± 61 μm. None of the cases showed extrusion, erosion, melt, or necrosis of the segments or corneal stroma. Mid-stromal depth implantation was also used in an attempt to achieve a greater influence on the anterior corneal curvature via a spacer effect. Again, further studies would be required to determine the effect of depth of placement of the CAIRS.

Eighteen patients underwent A-CACXL and 6 underwent A-CXL. Although an increased risk of complications has been reported in corneas steeper than 58.00 D, 11 eyes in our series had a steepest keratometry value of greater than 58.00 D, with the steepest being 67.40 D. None of these eyes showed an increased incidence of haze, scarring, or other complications. It is likely that the initial flattening created by the CAIRS made them suitable for safe subsequent CXL. At 1 month, the average steepest keratometry value had decreased from a mean preoperative value of 57.61 ± 5.42 D (range: 50.00 to 67.40 D) to 56.09 ± 4.60 D (range: 47.80 to 62.80 D). The A-CACXL technique was used for eyes receiving CXL with a corneal thickness of less than 400 μm after epithelial removal. The contact lens (90 μm thickness) and the subcontact lens riboflavin film contribute an average of 107.9 ± 9.4 μm32 additional functional thickness that, when added to a minimum intraoperative corneal thickness of greater than 300 μm of corneal stroma, raises the total functional corneal thickness to greater than 400 μm. Although we simultaneously cross-linked the segments and the keratoconic cornea after implantation to get the desired flattening effect, one of the drawbacks of our study was that we did not study how CXL affects the CAIRS or the effects of implanting ex vivo cross-linked segments. A future study that evaluates the effect of ex vivo CXL on the allogenic segment would therefore be desirable.

Despite the risk of complications being lower with allogenic tissue, a potential disadvantage includes the risk of stromal rejection. However, this was not noted in any eye in our series despite an early cessation of steroids within 5 weeks, unlike the norm in conventional allografts such as lamellar or full-thickness corneal grafts. Allogenic implants have been used extensively in the recent past for aphakia, hyperopia, keratoconus, and presbyopia,33–36 with a good safety and efficacy profile. The low volume of pure stromal transfer (without the more antigenic epithelium or endothelium) and the possibility of more rapid repopulation of the CAIRS by host keratocytes from the enclosing host stroma on all sides may contribute to a reduced risk of rejection. Processing of the implants with gamma irradiation may help further by deantigenizing the segments.37–40

A drawback of this study was the uniform nomogram that was used for all patients irrespective of the stage of keratoconus. Future studies will need to evaluate nomograms that change the thickness and arc length of the segments, as well as the optic zone and depth of implantation. Although optical grade donor corneas are not required for preparing the segments, non-edematous tissue is preferred to avoid difficulty in implantation. Eye bank involvement in processing, manufacture, preservation, and supply of preserved cornea/segments in the intermediate term (Optisol; Chiron Ophthalmics, Irvine, CA), long-term (organ culture), or very long-term (cryopreservation) storage can make availability easier in places with limited access to donor corneas. Ease of direct preparation of the segments by the surgeon is an advantage, as is biocompatibility.

This pilot study indicates that CAIRS implantation with CXL may be an advantageous option for patients with keratoconus in terms of simplicity, safety, efficacy, and stability. It avoids the use of synthetic tissue while retaining the effects on topography and surface regularization that are obtained by synthetic segments. Longer term studies are required to verify our initial results and to study the effects of nomograms and further customization. Studies directly comparing them with synthetic ICRS are also required. Future options include femtosecond laser–dissected, processed, cross-linked CAIRS, appropriate nomograms, and eye bank involvement for processing, storage, and supply of these segments.

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Comparison of Preoperative and Last Postoperative Visit Clinical Parameters (N = 24)

ParameteraValueDifference (95% CI)P
UDVA (decimal), mean ± SDb−0.14 (−0.21 to −0.08)< .001
  Preoperative0.22 ± 0.16
  Postoperative0.36 ± 0.22
CDVA (decimal), mean ± SDb−0.19 (−0.27 to −0.11)< .001
  Preoperative0.59 ± 0.21
  Postoperative0.79 ± 0.19
Spherical equivalent (D), mean ± SDb−4.07 (−5.91 to −2.33)< .001
  Preoperative−5.35 ± 3.17
  Postoperative−1.28 ± 5.61
Refractive astigmatism (D), mean ± SDb−0.71 (−1.53 to 0.11).087
  Preoperative−4.35 ± 1.53
  Postoperative−3.65 ± 2.18
Topographic astigmatism (D), mean ± SDb−0.89 (−1.52 to −0.27).007
  Preoperative−7.15 ± 3.14
  Postoperative−6.26 ± 3.72
Maximum keratometry (D), median (IQR)c1.70 (0.65 to 3.15)< .001
  Preoperative55.35 (50.40 to 60.60)
  Postoperative52.55 (48.25 to 56.70)
Steepest keratometry (D), mean ± SDb2.78 (1.55 to 4.02)< .001
  Preoperative57.61 ± 5.42
  Postoperative54.83 ± 4.33
Anterior best fit sphere (D), median (IQR)c1.00 (0.60 to 1.35)< .001
  Preoperative44.60 (43.60 to 47.45)
  Postoperative43.80 (43.05 to 46.80)
Posterior best fit sphere (D), median (IQR)c0.65 (−0.30 to 3.30).022
  Preoperative56.60 (54.70 to 59.75)
  Postoperative56.15 (53.20 to 57.00)
Mean power 3-mm zone (D), mean ± SDb1.76 (0.95 to 2.57)< .001
  Preoperative49.58 ± 3.46
  Postoperative48.10 ± 3.14
Mean power 5-mm zone (D), median (IQR)c2.25 (1.50 to 2.70)< .001
  Preoperative45.90 (44.60 to 48.85)
  Postoperative44.35 (42.45 to 46.25)
AS-OCT pachymetry (μm), mean ± SDc7.5 (−4.4 to 19.4).207
  Preoperative425.71 ± 47.07
  Postoperative418.21 ± 49.37

CXL Methods

ParameterA-CXL VariableA-CACXL Variable
Fluence (total) (J/cm2)5.45.4
Soak time and interval (minutes)30(q3)30(q3)
Intensity (mW)1010
Treatment time (minutes)99
Epithelium statusOffOff
ChromophoreRiboflavin (Peschke Trade GmbH, Switzerland)Riboflavin (Peschke Trade GmbH, Switzerland)
Chromophore carrierDextranDextran
Chromophore osmolarityIso-osmolarIso-osmolar
Chromophore concentration0.1%0.1%
Light sourceCL-UVR Rapid (Appasamy Associates, Chennai, India)CL-UVR Rapid (Appasamy Associates, Chennai, India)
Irradiation mode (interval)ContinuousContinuous
Protocol modificationsA-CXL(10*9)A-CXL(10*9), contact lens–assisted

Subgroup Analysis Between Eyes That Underwent Conventional A-CXL and A-CACXL

ParameteraPreoperativePostoperativeMean ChangeP
UDVA (decimal), mean ± SDb.279
  A-CACXL0.24 ± 0.150.41 ± 0.22−0.16 ± 0.16
  A-CXL0.12 ± 0.110.21 ± 0.09−0.09 ± 0.07
CDVA (decimal), mean ± SDb.442
  A-CACXL0.64 ± 0.20.85 ± 0.17−0.21 ± 0.2
  A-CXL0.47 ± 0.130.61 ± 0.09−0.14 ± 0.13
Spherical equivalent (D), mean ± SDb.57
  A-CACXL−4.42 ± 2.23−0.62 ± 4.46−3.64 ± 4.27
  A-CXL−8.13 ± 4.12−3.25 ± 8.43−4.88 ± 5.35
Refractive astigmatism (D), mean ± SDb.209
  A-CACXL−4.42 ± 1.64−3.42 ± 2.20−1.00 ± 1.91
  A-CXL−4.17 ± 1.29−4.33 ± 2.180.17 ± 1.91
Topographic astigmatism (D), mean ± SDb.61
  A-CACXL−7.19 ± 3.06−6.39 ± 3.27−0.80 ± 1.26
  A-CXL−7.03 ± 3.69−5.87 ± 5.19−1.17 ± 2.14
Maximum keratometry (D), median (IQR)c.089
  A-CACXL55.60 (50.40 to 60.10)52.70 (49.10 to 55.40)2.35 (0.90 to 3.20)
  A-CXL53.75 (47.10 to 63.50)52.45 (47.40 to 62.90)0.65 (−0.30 to 1.90)
Steepest keratometry (D), mean ± SDb.707
  A-CACXL57.78 ± 4.5354.87 ± 4.242.92 ± 2.88
  A-CXL57.12 ± 8.1054.73 ± 4.992.38 ± 3.27
Anterior best fit sphere (D), median (IQR)c.217
  A-CACXL44.60 (43.80 to 47.40)43.75 (43.20 to 46.60)0.90 (0.50 to 1.30)
  A-CXL45.25 (42.90 to 48.80)44.50 (41.90 to 47.00)1.30 (1.00 to 1.80)
Posterior best fit sphere (D), median (IQR)c.99
  A-CACXL56.60 (54.50 to 59.30)56.40 (54.40 to 57.00)0.35 (−0.20 to 3.40)
  A-CXL56.80 (54.90 to 61.90)54.10 (52.20 to 56.70)2.55 (−1.40 to 3.20)
Mean power 3-mm zone (D), mean ± SDb.66
  A-CACXL49.84 ± 2.9047.98 ± 2.941.86 ± 2.05
  A-CXL49.92 ± 5.1748.47 ± 3.961.45 ± 1.63
Mean power 5-mm zone (D), median (IQR)c.349
  A-CACXL45.90 (44.80 to 48.60)44.35 (42.70 to 46.20)2.15 (1.40 to 2.60)
  A-CXL46.55 (44.30 to 50.50)45.25 (42.20 to 47.40)2.55 (2.20 to 3.10)
AS-OCT pachymetry (μm), mean ± SDc.790
  A-CACXL413.94 ± 48.48406.67 ± 50.452.5 (−12 to 35)
  A-CXL461 ± 14.46452.83 ± 25.298.5 (3 to 11)
Authors

From Dr. Agarwal's Refractive and Cornea Foundation, Chennai, India (SJ, SRP, AR, AIS); and Dr. Agarwal's Group of Eye Hospitals, Chennai, India (SJ, SRP, AA, AR, AIS, JMR).

Dr. Jacob has a patent pending for shaped corneal segments and devices and processes used to manufacture them. The remaining authors have no financial or proprietary interest in the materials presented herein.

The authors thank Asha Jacob for technical and writing assistance and Mr. Sambath for data collection.

AUTHOR CONTRIBUTIONS

Study concept and design (SJ, AA); data collection (SRP, AR, AIS); analysis and interpretation of data (SJ, SRP, AR, AIS, JMR); writing the manuscript (SJ, SRP, AR, AIS, JMR); critical revision of the manuscript (SJ, AA); statistical expertise (JMR); administrative, technical, or material support (SRP, AR, AIS); supervision (AA)

Correspondence: Amar Agarwal, MS, FRCS, FRCO, Dr. Agarwal's Eye Hospital and Eye Research Centre, 19, Cathedral Road, Chennai 600086, India. E-mail: dragarwal@vsnl.com

Received: October 03, 2017
Accepted: January 22, 2018

10.3928/1081597X-20180223-01

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