• CXL + Topo guided PRK

*Eyesight and Imaging - Advances and New Perspectives*

Due to the epithelial debridement is a major contributor to the postoperative complications of CXL, such as infective keratitis and an abnormal wound-healing response [37]. This issue has perpetuated interest in epithelium-on technique. Epi-on CXL has less discomfort to the patient and reduces postoperative complications [43]. This CXL technique has low complication rate, 0% to 3.9% of the patients has only transient haze [37]. According to the hydrophilic property of riboflavin solution, the penetration through the intact hydrophobic corneal epithelium is difficult. The standard formulations show minimal penetration through intact epithelium. The modifications by adding various additives, such as benzalkonium chloride, topical anesthetic, tris(hydroxymethyl) aminomethane (trometamol), sodium ethylenediaminetetraacetic acid, have been proposed to improve epithelial permeability to riboflavin [36]. Riboflavin penetration can be improved by increased riboflavin concentration and iontophoresis [36]. Since even the low amount of riboflavin surface films will markedly block UV-A transmission, transepithelial formulations are often rinsed from epithelial surface before irradiation [36]. The iontophoretic delivery system uses of mild electrical current for delivering riboflavin through the epithelium [36]. It allows greater and deeper riboflavin penetration in the corneal stroma than the conventional epithelium-on technique. Overall, the effectiveness of transepithelial techniques has been disappointing [27]. Epi-on CXL has limited keratocyte apoptosis, shallower demarcation line and less biomechanical rigidity than standard epi-off CXL [37]. In general, better outcomes can be achieved by standard epithelium off technique and epi-on CXL have resulted in progression of the disease after treatment [36, 44]. However, recent research with innovative transepithelial CXL system achieved 4-fold higher corneal stromal concentrations of riboflavin than commercially available epi-on CXL system, and this level is theoretically adequate

Due to the presence of oxygen is required for CXL, but high-exposure doses of UVA light cause a decrease in the oxygen concentration rapidly [45]. The recent technique has focused on pulsing the UVA light with "on" and "off" periods to increase the efficacy of CXL treatment by replenishing the consumed oxygen [46]. This technique is an effective treatment modality to stop progression in progressive

Despite the fact that CXL can halt the progression of keratoconus and provide corneal stability, functional visual acuity remains a problem [47]. Recent data from the systematic review disclosed that conventional epi-off CXL can flattening cornea 2 D approximately and improving visual acuity 2 lines or 10 letters on average [48]. CXL normalizes the corneal shape by changing the physical properties of the cornea, resulting in reduction of all corneal aberrations, high order and low order. The improvement in uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) are related to improvement in the total corneal aberrations

In order to address this issue, CXL can be performed alone or in combination with topo guided photorefractive keratectomy (PRK), ICRS, phakic IOLS or Topo

guided PRK plus ICRS for better improvement of visual acuity [15].

*5.2.1.2 Epi-on CXL/transepithelial CXL*

for effective CXL [44].

*5.2.1.4 CXL plus*

*5.2.1.3 Pulsed-light accelerated CXL (PLA-CXL)*

keratoconus but regresses some of the cases [46].

and only high-order aberrations respectively [49].

**46**

Kanellopoulos et al. reported the first case of topography-guided PRK performed 1 year after CXL for treatment of keratoconus and showed visual acuity improvement [50]. On the contrary, the Athens protocol which combines accelerated UV-CXL with same-day photorefractive keratectomy (PRK) was more effective with improvement in UDVA and CDVA of 20/45 or better (2.25 logMAR) was founded in 83% of patients at last follow up [51]. However, this study was conducted in post-LASIK ectasia [51]. Same-day simultaneous topography guided PRK CXL in progressive keratoconus appears to be superior to sequential CXL with later PRK (6 months later) in the aspect of UCVA, BSCVA, spherical equivalent (SE) and mean reduction in K [52]. This combined technique also prevents regression of keratoconus and reduce the risk of keratectasia and might be suitable for eyes requiring improvements in irregular astigmatisms but still have good CDVA [47, 53].

### • CXL + ICRS

The CXL can be performed before, simultaneously or after the ICRS. The advantage of performing the CXL first is slowing the progression of the keratoconus and selects the best alternative way to treat the residual refractive error [54]. The recent systematic review and meta-analysis demonstrated that simultaneous ICRS implantation and CXL may provide better outcomes in term of refraction and keratometry. However, UDVA, BCVA and cylindrical refractive error were similar between combined technique and staged procedure [55]. The combined procedure of CXL plus ICRS implantation appears safe and efficacious for the treatment of progressive keratoconus with significant improvements in visual acuity, keratometry values, and refractive error [54]. This technique might be effective for eyes with more irregular astigmatism and worse CDVA [53].

• CXL + Topo guided PRK + phakic IOLS

The simultaneous topography-guided photorefractive keratectomy (PRK) and crosslinking (Athens protocol) followed by phakic intraocular lens (IOL) implantation 2–4 months later for managing keratoconus improved and stabilized visual performance in patients with keratoconus. The Kmean, SE, UDVA, CDVA improved significantly. At last follow-up, all eyes could achieve CDVA of 0.3 or better [56].

• CXL + ICRS+ + phakic IOLS

Three steps treatment of keratoconus by ICRS implantation, CXL and phakic IOLS significantly improve UDVA, CDVA, higher order aberrations and corneal shape in moderate to severe keratoconus [57]. Moreover, keratometry (Ksteep, Kflat, Kmax) and refraction (sphere, SE, but not cylinder) were also improved [58]. The time interval between ICRS implantation and CXL was 4–6 weeks and ICL implantation was performed 6–8 months after CXL [57, 58].

#### *5.2.1.5 CXL in thin cornea*

The 0.1% riboflavin in 20% dextran solution is used in original Dresden protocol. Only the anterior 300 μm of stroma can be treated [38, 59]. This standard technique requires corneal pachymetry more than 400 μm after deepithelization to decrease complications such as corneal stromal scar and corneal endothelial cytotoxicity [47, 60]. In order to combat this issue, there are various modifications to the conventional CXL protocol for CXL in thin cornea. These modifications include hypoosmolar riboflavin, transepithelial CXL, iontophoresis-assisted CXL, Customized epithelial debridement technique, Lenticuleassisted CXL, contact-lens- assisted CXL (CACXL) and individualized corneal CXL [60–67].

Hypoosmolar riboflavin has lower colloidal pressure (310 mOsmol/L vs. 402.7 mOsmol/L in isotonic riboflavin) that causes stromal swelling to double its thickness where stromal bed is less than 400 μm [60]. However, the efficacy of CXL using hypoosmolar riboflavin was lower than traditional CXL with isotonic riboflavin. The possible theory to explain is that in hydrated corneas (using hypoosmolar riboflavin) concentration of collagen fibrils is decreased, hence fewer collagen fibrils are available for CXL [60, 61]. By changing the osmolarity of the riboflavin solution, while maintaining the concentration at 0.1%, probably does not alter the final riboflavin concentration in the cornea. On the contrary, modifying other parameters to obtain a more shallow depth of treatment; ie, the intensity of the UVA light, the duration of treatment, or the intensity of riboflavin concentration will alter the final riboflavin concentration in the cornea and require new dose–response assays [61]. Unfortunately, these modified techniques have not yet distinguished themselves as more effective than any other in terms of topographic or visual outcomes.

Despite the fact that CXL has a promising clinical outcomes, risk factors for ongoing ectasia include the application of isotonic riboflavin solution to thicken a thin cornea prior to treatment, corneas steeper than 58 D and age > 35 years [18, 68]. The most frequent definition of treatment failure is the continual progression of keratoconus with an enhancement of Kmax reading of 1.0 D 0r 1.5 D over the preoperative value [40, 47]. The outcomes of different CXL techniques are listed as in **Table 4**.

#### *5.2.2 Intrastromal corneal ring segments (ICRS)*

Intrastromal corneal ring segments (ICRS) were FDA-approved in 1999 for the treatment of low myopia. ICRS implantation causes displacement of the collagen fibers resulting in flattening of the central cornea and tissue adjacent to the ring is displaced forward [37]. ICRS are segments of polymethylmethacrylate (PMMA) plastic available in numerous arc-lengths, thicknesses, and designs. Five types of ICRS are available for keratoconus: 1) Intacs (Addition technology Inc.) 2) Intacs SK (Addition technology Inc.), 3) Ferrara Rings (Ferrara ophthalmics) and 4) Keraring (Mediphacos).5). MyoRing (Dioptex, GmbH, Linz, Austria). The devices are inserted into stromal tunnels that may be created manually using a corkscrew blade or femtosecond laser with no difference in results (except that channels tend to be slightly shallower when created manually and more often decentered when created by laser) [37]. The objective of ICRS implantation is to improve visual and topographic outcomes and restoration of contact lens tolerance [15, 18, 37]. Maximal flattening effect occurs with segments at 60–79% corneal thickness. Shallower than 60%, the effect may be lessened and can induced ocular surface complications. On the contrary, deeper than 80%, there may have no topographic effect [88]. The outcome achieved is directly proportional to the thickness of the ICRS and inversely proportional to its diameter [37]. ICRS can be used alone or used in combination with other treatment options such as CXL for stabilizing disease progression [15]. The outcomes of ICRS are listed as in **Table 4**.

Although, ICRS has good visual and topographic results, some complications have been reported. Intraoperative complications rate are low, but can occur and

**49**

**Treatment** **Standard CXL**

• •

Corneas steeper than 58 D, no

benefit in UDVA or BCVA [68]

VA either remains unchanged or improves by 1–2 lines [18, 38, 48, 49]

**Visual outcomes**

**Refractive outcomes**

•

Small reduction in

• • [18, 38, 48, 49]

astigmatism <0.5 D [18,

70]

•

variable, unpredictable

corneal astigmatic cor-

• •

advanced KC may demonstrate changes

more frequently than mild disease [18]

Shortly after therapy, CCT may decline

till 3 months but rebounds to baseline at

1 year [39]

KFlat did not change [49]

rection [71]

•

Sphere and cylinder was

less negative, SE was

more positive [49]

**Epi-on CXL/** 

•

Improvement of UDVA and

•

No changes for the

•

Less effective than standard CXL to

•

23–55% progression of the

disease between

1 year- 3 years after treatment

[44, 69, 73]

•

Stop progression 50% in pediatric patient with Iontophoretic

Transepithelial CXL [63]

reduce Kmax (mean difference = 1.05D)

sphere, cylinder, and SE

up to 12 months after

[62]

•

Kmax was reduced by 1.9–2.2 D,1 and

3 months after CXL but not later [49]

CXL. [49]

• CXL [69]

•

Stable Kmax (no flattening)or Kmax

increase by 1.1 D [69, 73]

•

Similar increase refractive cylinder by 1.5 D and

spherical refraction by

•

Kmin was reduced by 0.6 to 0.8 D, 1 and

3 months after CXL, and not later [49]

Ksteep was reduced by 1.9 and 1.2 D, 6

and 12 months, respectively, after CXL.

[49]

• •

Kflat, Ksteep increase slightly overtime

(but decrease slightly overtime in

standard CXL) [69]

•

Similar change in CCT with standard

CXL or stable CCT [62, 69]

Kavg was not changed [49]

1.0 D as standard CXL

•

[69]

Lower SE than standard

CDVA (logMAR) [49]

**Transepithelial** 

**CXL**

• •

6 months: 0.17

12 months: 0.05

• CXL [69]

•

Similar or lower UDVA with

standard CXL [62, 69]

0.07 logMAR more improvement in CDVA than standard

3 months: 0.06

•

**Topographic outcomes**

Evening out of corneal parameters and a

decline in overall surface variability [72]

Flattening Kmean and Kmax by 1–2 D

•

Stop progression 75% in

pediatric patient [63]

**Disease progression**

•

Stop progression

> 90% -100% [68, 69, 74]

*Keratoconus Treatment Toolbox: An Update DOI: http://dx.doi.org/10.5772/intechopen.94854*


## *Keratoconus Treatment Toolbox: An Update DOI: http://dx.doi.org/10.5772/intechopen.94854*

*Eyesight and Imaging - Advances and New Perspectives*

CXL [60–67].

or visual outcomes.

are listed as in **Table 4**.

*5.2.2 Intrastromal corneal ring segments (ICRS)*

The outcomes of ICRS are listed as in **Table 4**.

endothelial cytotoxicity [47, 60]. In order to combat this issue, there are various modifications to the conventional CXL protocol for CXL in thin cornea. These modifications include hypoosmolar riboflavin, transepithelial CXL, iontophoresis-assisted CXL, Customized epithelial debridement technique, Lenticuleassisted CXL, contact-lens- assisted CXL (CACXL) and individualized corneal

Hypoosmolar riboflavin has lower colloidal pressure (310 mOsmol/L vs. 402.7 mOsmol/L in isotonic riboflavin) that causes stromal swelling to double its thickness where stromal bed is less than 400 μm [60]. However, the efficacy of CXL using hypoosmolar riboflavin was lower than traditional CXL with isotonic riboflavin. The possible theory to explain is that in hydrated corneas (using hypoosmolar riboflavin) concentration of collagen fibrils is decreased, hence fewer collagen fibrils are available for CXL [60, 61]. By changing the osmolarity of the riboflavin solution, while maintaining the concentration at 0.1%, probably does not alter the final riboflavin concentration in the cornea. On the contrary, modifying other parameters to obtain a more shallow depth of treatment; ie, the intensity of the UVA light, the duration of treatment, or the intensity of riboflavin concentration will alter the final riboflavin concentration in the cornea and require new dose–response assays [61]. Unfortunately, these modified techniques have not yet distinguished themselves as more effective than any other in terms of topographic

Despite the fact that CXL has a promising clinical outcomes, risk factors for ongoing ectasia include the application of isotonic riboflavin solution to thicken a thin cornea prior to treatment, corneas steeper than 58 D and age > 35 years [18, 68]. The most frequent definition of treatment failure is the continual progression of keratoconus with an enhancement of Kmax reading of 1.0 D 0r 1.5 D over the preoperative value [40, 47]. The outcomes of different CXL techniques

Intrastromal corneal ring segments (ICRS) were FDA-approved in 1999 for the treatment of low myopia. ICRS implantation causes displacement of the collagen fibers resulting in flattening of the central cornea and tissue adjacent to the ring is displaced forward [37]. ICRS are segments of polymethylmethacrylate (PMMA) plastic available in numerous arc-lengths, thicknesses, and designs. Five types of ICRS are available for keratoconus: 1) Intacs (Addition technology Inc.) 2) Intacs SK (Addition technology Inc.), 3) Ferrara Rings (Ferrara ophthalmics) and 4) Keraring (Mediphacos).5). MyoRing (Dioptex, GmbH, Linz, Austria). The devices are inserted into stromal tunnels that may be created manually using a corkscrew blade or femtosecond laser with no difference in results (except that channels tend to be slightly shallower when created manually and more often decentered when created by laser) [37]. The objective of ICRS implantation is to improve visual and topographic outcomes and restoration of contact lens tolerance [15, 18, 37]. Maximal flattening effect occurs with segments at 60–79% corneal thickness. Shallower than 60%, the effect may be lessened and can induced ocular surface complications. On the contrary, deeper than 80%, there may have no topographic effect [88]. The outcome achieved is directly proportional to the thickness of the ICRS and inversely proportional to its diameter [37]. ICRS can be used alone or used in combination with other treatment options such as CXL for stabilizing disease progression [15].

Although, ICRS has good visual and topographic results, some complications have been reported. Intraoperative complications rate are low, but can occur and

**48**


**51**

**Treatment** **Intrastromal corneal ring segments (ICRS)**

**Visual outcomes**

• and BCVA

•

Newer segment designs such

as INTACS SK and Kerarings,

•

Significant changes

between 6 and 12 months

visual gains still rarely exceed

1–2 lines and may increase

•

Full refractive effect is

not seen before 1 year

postoperatively

•

Appears stable, at least

through 10 years of

follow-up [18]

**Penetrating** 

• •

BCVA 20/30 to 20/40 [18]

UDVA 20/50 to 20/100 [18]

•

Average astigmatism 3

Donor button is

Approximately 10% of eyes will

display recurrent KC 20 years after

PK; some diseased recipient cornea is

left unremoved [84, 85]

• •

same-sized; mean K around 42.5 D [18]

oversized 0.5 mm; mean K around 45.5 D

to 5 D but may exceed 10

D [18]

•

20% require refractive

surgery after surgery [18]

•

Suture removal tends to

result in large unpredictable swings in the amount of astigmatism

**Deep Anterior** 

•

Descematic DALK; Similar/

•

Same refractive outcomes or more myopia

2 D steeper than if they had received a similarly

NA

sized PK [18]

than PK [18, 82]

better UDVA, BSCVA, BCVA to

PK [18, 81]

**Lamellar** 

**Keratoplasty** 

**(DALK)**

•

Pre-descematic DALK; inferior

visual results to PK

• PK [18]

Fewer higher aberrations than

**keratoplasty** 

**(PK)**

visual aberrations. [18]

•

10% lost ≥1 line of UDVA, and

20% lost ≥1 line of BCVA [80]

Improve 1–2 lines of BSCVA

•

Sizable reduction in

• D [18]

•

INTACS SK, Kerarings, Ferrara ring,

and Myoring reduce mean Ks by 2–9

D (smaller internal diameters and are

placed closer to the corneal center) [18]

corneal astigmatism

from 1 to 3 D

**Refractive outcomes**

**Topographic outcomes**

Standard INTACS reduce mean Ks by 3–5

**Disease progression**

Stop progression >90% for mild to

moderate KC at 5 and 10 years

[68, 80, 83]

*Keratoconus Treatment Toolbox: An Update DOI: http://dx.doi.org/10.5772/intechopen.94854*


### *Keratoconus Treatment Toolbox: An Update DOI: http://dx.doi.org/10.5772/intechopen.94854*

*Eyesight and Imaging - Advances and New Perspectives*

**50**

**Treatment** **Accelerated CXL**

•

No improvement in UDVA,

•

Similar reduction in

•

astigmatism by 0.8–0.9

D, SE by 0.9 D when

compare to standard

•

Greater reduction in Kmean than

standard CXL [78]

CXL at 4 years [76]

•

Cylinder increased by 0.7

•

Epi-on was less effective than Epi-off

Accelerated CXL to reduce Kmean, Kmax

D 3 months after CXL,

SE was more positive

[75]

• •

Epi-off: decreased during the first

6 months and return to baseline at 1 year

[75]

•

Less or similar corneal thinning than

standard CXL [78, 79]

•

No significant changes in corneal

topography parameters [49]

**Pulsed-Light** 

•

CDVA improved by 0.11

•

Corneal astigmatism

• •

Flattening of Kmean and Kmax by 0.58

and 0.75 D at 2 years [46]

•

Thinnest corneal pachymetry reduced by

7–16 μm at 1–2 years [46, 77]

•

CCT reduced by 6 μm at 2 years

Kmax reduced by 1.2D at 1 year [77]

All eyes show stability of Kmax,

30% show small increase in Kmax at

12 months [77]

increased by 0.3 D at

1 year [77]

logMAR at 6 months [49]

•

BCVA improved by 0.2 logMAR

at 1 year [77]

•

BSCVA improved by 0.17

logMAR at 2 years [46]

**Accelerated CXL**

Epi-on: stable CCT

after 36 months by 1.07

D, sphere data were not

reported [49]

BCVA [49]

• •

Compare to standard CXL at

5 years [76]

•

Similar improve in UDVA by

0.o8 logMAR

•

Similar improve in BCVA by

0.06 logMAR

UDVA and BCVA increased 1

Snellen line at 30 months [75]

**Visual outcomes**

**Refractive outcomes**

**Topographic outcomes**

Similar reduction in K with standard CXL

(Kflat, Ksteep Kmean by 1 D and Kmax

by 1.7–2.2 D, at 5 years) [49, 76]

**Disease progression**

Conflicting findings [75]


**Table 4.**

**53**

than PK [15].

*Keratoconus Treatment Toolbox: An Update DOI: http://dx.doi.org/10.5772/intechopen.94854*

period [89].

*5.2.3 Corneal transplantation*

*5.2.3.1 Penetrating keratoplasty (PK)*

required over their lifetime ultimately [18].

*5.2.3.2 Deep anterior lamellar keratoplasty (DALK)*

usually relate to corneal tunnel creation such as insufficient tunnel depth, asymmetry or decentration, or Bowman's layer perforation [15]. The post-operative complications have been reported such as corneal neovascularization, keratitis, deposits around ring segment, corneal haze, halos, pain, corneal melting or edema, segment extrusion, visual fluctuation, and photophobia [15]. This procedure is reversible and not preclude from further surgeries such as CXL and/or corneal transplantation. Due to complications such as stromal necrosis, segment extrusion of synthetic ICRS material, corneal allogenic ICRS (CAIRS) combined with CXL has been reported. Instead of using PMMA to create segment, CAIRS is trephined from donor cornea. CAIRS were implanted into mid-depth corneal tunnel that was created by femtosecond laser, followed by ACXL [89]. This procedure has a promising result in term of improvement of UDVA by 2.79 lines, CDVA by 1.29 lines. Moreover, this procedure demonstrated improvement of SE, Kmax, Ksteep and topographic astigmatism and halt progression in all cases during follow

Treatment options for advanced keratoconus that has corneal thickness less than 400 μm, Kmax more than 58 D may be limited to corneal transplantation that can stabilize the cone and enable continued contact lens wear [86]. The keratoplasty techniques may be penetrating keratoplasty (PK), Deep Anterior Lamellar

Penetrating or lamellar keratoplasty techniques are used depending on the extent of corneal scarring [15]. PK provides long term good vision but has slow visual rehabilitation from residual astigmatism and anisometropia [15]. Both PK and DALK tend to worsen any existing ocular surface problems, as both involve surface incisions, injury of corneal nerves, placement of long-lasting sutures, and requiring post-operative topical corticosteroids [18]. Despite the facts that long term graft survival following PK for keratoconus is good, averaging 97% at 5 years, 90% at 10 years and 80% at 20–25 years, most of the patients with advanced KC are transplanted early in life, therefore it is more likely that more than one graft may be

The visual outcomes of BCVA, UDVA for DALK remains debated. The recent data from systematic review and meta-analysis demonstrated that the visual outcomes were worse [90] or better [81] than those for PK. The outcomes of DALK for keratoconus are better than PK [81] or equivalent [81] in terms of refractive error, astigmatism and rejection rate. Fifty percent of eyes may encounter Descemet membrane perforation which is the most significant intra-operative complications [18]. Other complications such as a double anterior chamber and persistent corneal edema have been reported. DALK may be less prone to secondary ocular hypertension because of their lower steroid requirement (owing to the smaller risk of rejection) [18]. Another advantage DALK is the lack of endothelial rejection because there is no endothelial defense reaction [15]. The reported rates of postoperative complications such as graft rejection, secondary glaucoma, complicated cataracts, and constant endothelial cell loss are lower with DALK

Keratoplasty (DALK) or Bowman layer transplantation.

*Outcomes of surgical treatment of keratoconus.*

#### *Keratoconus Treatment Toolbox: An Update DOI: http://dx.doi.org/10.5772/intechopen.94854*

*Eyesight and Imaging - Advances and New Perspectives*

**52**

**Treatment** **Bowman layer** 

• 1–2 lines

•

BCVA usually remains

unchanged [18]

BSCVA typically improves by

•

Slight hyperopic shift

• Ks 5 D

• • • pachymetry [86]

•

These topographic changes occur within

the first post-operative month and appear

stable through at least 2 years

*CXL = Corneal collagen cross-linking, PRK = Photorefractive keratectomy, IOL = intraocular lenses, UDVA = Uncorrected Distance visual acuity, CDVA = Corrected Distance visual acuity, BCVA = Best* 

*Corrected Visual Acuity, BSCVA = Best Spectacles Corrected visual acuity, D = Diopter, SE = spherical equivalent.*

**Table 4.**

*Outcomes of surgical treatment of keratoconus.*

*Other than standard CXL, formulation of riboflavin solutions, riboflavin concentration, total UVA energy that was used for each study may be different.*

Non- significantly increase CCT, thinnest

K max 8–9-D [86, 87]

max corneal power 5 to 7 D

with no significant effect

on corneal astigmatism

[86, 87]

**transplantation**

**Visual outcomes**

**Refractive outcomes**

**Topographic outcomes**

Mean reduction in anterior simulated

**Disease progression**

• •

90% [87]

Stop progression

usually relate to corneal tunnel creation such as insufficient tunnel depth, asymmetry or decentration, or Bowman's layer perforation [15]. The post-operative complications have been reported such as corneal neovascularization, keratitis, deposits around ring segment, corneal haze, halos, pain, corneal melting or edema, segment extrusion, visual fluctuation, and photophobia [15]. This procedure is reversible and not preclude from further surgeries such as CXL and/or corneal transplantation. Due to complications such as stromal necrosis, segment extrusion of synthetic ICRS material, corneal allogenic ICRS (CAIRS) combined with CXL has been reported. Instead of using PMMA to create segment, CAIRS is trephined from donor cornea. CAIRS were implanted into mid-depth corneal tunnel that was created by femtosecond laser, followed by ACXL [89]. This procedure has a promising result in term of improvement of UDVA by 2.79 lines, CDVA by 1.29 lines. Moreover, this procedure demonstrated improvement of SE, Kmax, Ksteep and topographic astigmatism and halt progression in all cases during follow period [89].
