Preoperative Evaluation of Keratoconus and Ectasia

Introduction

In the last 2 decades, the clinician’s ability to diagnose keratoconus has increased. This is due to the knowledge and development of diagnostic instruments for keratoconus, from corneal topography to the more recent corneal tomography. The advances in surgical treatments for keratoconus are a logical consequence of this evolution. Several alternative procedures have been proposed to delay or prevent the need for penetrating keratoplasty (PK), such as the use of the intracorneal ring segment (ICRS); corneal cross-linking (CXL); therapeutic excimer laser treatments, including phototherapeutic keratectomy and photorefractive keratectomy (PRK), and phakic intraocular lenses (PIOL) alone or in combination; and small incision lenticle extraction (SMILE). Other keratoplasty techniques have been developed, such as deep anterior lamellar keratoplasty (DALK) and femtosecond (FS) laser-assisted corneal transplantation. These latter strategies, as well as PK, have had complications, such as allograft rejection, suture problems, healing disturbances, disease progression in the recipient tissue, and difficulties in visual rehabilitation caused by irregular postoperative astigmatism. All of these factors contribute to choosing keratoplasties as the last resource.

Decreased spectacle corrected visual acuity and contact lens intolerance are two important elements that must be considered to indicate surgical intervention in a patient with keratoconus. The purpose of this chapter is to describe the preoperative evaluation of these different techniques.

Guidelines for Preoperative Examination

The preoperative ophthalmologic evaluation of patients with keratoconus shares elements between different surgical techniques. Different patient characteristics need to be analyzed to determine the best surgical choice. General health evaluation is the first step in the preoperative approach since most procedures are performed under local or topical anesthesia. A thorough clinical history is very important, as it may help gather valuable information related to corneal pathology. Specifically, the visual history during the patients’ life can provide information regarding amblyopia, retinal disease, optic neuropathy, or glaucoma.

The first steps of preoperative clinical examination include visual acuity and refraction. Contact lens wear is an important factor to consider in order to obtain a reliable measurement of visual acuity, refraction, pachymetry, and topographic evaluation. Patients should be required not to wear them for 1 week in the case of soft contact lenses and at least 3 weeks in the case of hard contact lenses. Uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) must be recorded. Adnexal evaluation must rule out any eyelid or lacrimal disorders and, if they are present, they must be treated before surgery. A healthy ocular surface is needed for a successful procedure. The evaluation of the tear film includes measurement of the tear meniscus, Schirmer test, and tear film break up time.

At slit lamp examination, the cornea should be examined to analyze its curvature, transparency, and thickness. If it is too opaque for a good anterior segment exploration, an ultrasound biomicroscopy or ocular coherence tomography must be performed. This is important regarding the outcomes: the better the condition of the anterior segment, the more probability of surgical success.

Intraocular pressure should be measured in every patient, either by applanation tonometry or (in very steep corneas with keratoconus) with noncontact tonometry. Due to the frequent association of keratoconus and atopy, steroid-induced glaucoma is not unusual in these patients. Ocular pressure (or glaucoma, if present) must be controlled before surgery. A combined surgery could be performed if needed.

Dilated ophthalmoscopy is mandatory; in the case of opaque media, ocular fundus must be evaluated by B-scan ultrasonography. Other tests that help to exclude other retinal or optic nerve diseases include color vision testing, electrophysiologic tests, visual fields, and retinal angiography.

Corneal Cross-Linking

Corneal cross-linking (CXL) is a procedure used to increase the biomechanical rigidity of the corneal tissue. It is a new technique that has been used to halt the progression of ectactic diseases, with low complication rates. It uses riboflavin and ultraviolet A light to enhance the corneal biomechanics through increasing the degree of covalent bonding between collagen fibrils and proteoglycans.

Definition of Progression

CXL has been indicated in keratoconus patients that have had progression; some authors propose treating all patients with keratoconus without documenting progression because the benefits exceed the risks. It has been difficult to define progression; therefore we do not have an established value because there are many definitions for it. Different definitions of keratoconus progression are shown in Table 12.1 . The indications and contraindications of CXL are shown in Table 12.2 .

TABLE 12.1

Different Definitions of Keratoconus Progression

Progression Definition
Mastropasqua	Vazirani et al. Definition	Keratoconus Global Consensus
• Kmax increase > 1 D over a year • Change of myopia or astigmatism ≥ 3 D in 6 months • Kmean change ≥ 1.5 D in 3 consecutive topographies over 6 months • Decrease in corneal thickness of ≥ 5% in 6 months	• Kmax ≥ 1 D increase • Kmax− Kmin ≥ 1 D increase • Kmean ≥ 0.75 D increase • Pachymetry ≥ 2% decrease in central corneal thickness • Corneal apex power > 1 D increase • Spherical equivalent > 0.5 D change	(At least two of the following parameters) • Steepening of the anterior corneal surface • Steepening of the posterior corneal surface • Thinning or an increase of corneal thickness change from the periphery to the thinnest point Documented over time and must be consistent.

TABLE 12.2

Cross-Linking Indications and Contraindications

CXL Indications	CXL Contraindications
• Progressive keratoconus • All ages • Combined procedures	• Corneal thickness < 400 µm * • Prior herpetic infection • Severe corneal scarring • History of inadequate wound healing • Ocular surface disease • Autoimmune disorders • Pregnancy • Breastfeeding

CXL, Cross-linking.

* Standard Dresden Protocol.

Corneal Cross-Linking Techniques Guideline

The Dresden protocol consists of epithelial removal with application of 0.1% riboflavin solution for 30 minutes followed by 30 minutes of UVA irradiation with a power of 3 mW/cm. Some authors have reported stabilization or flattening of corneal keratometries and stabilization or improvement of visual acuity after standard CXL.

Patients with progressive advanced keratoconus will usually present with thin corneas. The Dresden protocol establishes a corneal limit of 400 µm and involves the removal of epithelium followed by the instillation of iso-osmolar 0.1% riboflavin solution in 20% dextran. For thinner corneas (< 400 µm after epithelium removal) cross-linking can result in significant risk of endothelial cell damage; thus hypo-osmolar riboflavin has been proposed as an option for thin corneas, achieving a thickness increase of approximately 70 µm after 1 minute of instillation that remained stable for about 22 minutes. Hypo-osmolar riboflavin 0.1% solution was generated by diluting vitamin B2-riboflavin-5-phosphate 0.5% with physiological salt solution (sodium chloride 0.9% solution). Hypo-osmolar riboflavin solution does not contain dextran. It is known that de-epithelialized corneas can swell up to two times their normal thickness when irrigated with a hypo-osmolar solution; thus this method has been used in CXL. Corneas are irrigated with hypo-osmolar riboflavin until the corneal thickness reaches 400 µm. Another proposed option for thin corneas is to perform CXL with custom pachymetry-guided epithelial debridement, leaving epithelium on the thinnest area, but further research is needed to prove its safety and efficacy. A viable option for thin corneas is the use of a 90-µm soft contact lens immersed in iso-osmolar 0.1% riboflavin in dextran for 30 minutes before applying it on the de-epithelialized cornea. The advantage of this method is that it is not dependent on corneal swelling and will not cause endothelial damage; even though surface irradiance is reduced about 40% to 50% and oxygen diffusion may be decreased by the contact lens. Accelerated CXL has been used in thin corneas without endothelial loss;for better results, the use of pulsed CXL has been shown to have a higher effect owing to optimization of oxygen availability.

Photrexa (Avedro) formulations combined with the KXL device (Avedro) have been approved by the US Food and Drug Administration (FDA). This is an epi-off CXL, and either one of two riboflavin solutions: Photrexa (riboflavin 5′-phosphate ophthalmic solution 0.146%) and Photrexa Viscous (riboflavin 5′-phosphate in 20% dextran ophthalmic solution 0.146%).

Clinical Evaluation

Preoperative evaluation for CXL patients should include UCVA, biomicroscopy (emphasis on ocular surface integrity and severe corneal scarring), manifest refraction (actual and previous), topography (actual and previous), BCVA, intraocular pressure, and corneal thickness.

Topography Evaluation

One of the most critical preoperative values to measure is corneal thickness, either by corneal tomography or ultrasound pachymetry. This parameter indicates whether CXL is a suitable option. Additionally, keratometric values and different corneal indices will help to assess surgery success during follow-up.

Prognostic Factors

It has been demonstrated that eccentric cones are associated with higher keratometric values 1 year after CXL treatment. Patients with lower preoperative visual acuity had a greater improvement in visual acuity after CXL treatment.

It has been postulated that steeper corneas would be flatter after CXL, rarely exceeding 2 diopters (D), but it is also known that corneas steeper than 58 D would have greater risk of progression especially if the cone is eccentric; and an increased risk of decreased vision with K > 55 D.

Patients should be advised that the treatment failure rate ranges from 8.1% to 33.3% (continued progression with Kmax readings increasing more than 1 D). It is important to explain that, in most cases, CXL by its own is not a refractive procedure. However, the earlier the treatment is done, the better results for the patient because it is a procedure that prevents ectasia complications rather than fixing them.

Definition of Progression

CXL has been indicated in keratoconus patients that have had progression; some authors propose treating all patients with keratoconus without documenting progression because the benefits exceed the risks. It has been difficult to define progression; therefore we do not have an established value because there are many definitions for it. Different definitions of keratoconus progression are shown in Table 12.1 . The indications and contraindications of CXL are shown in Table 12.2 .

TABLE 12.1

Different Definitions of Keratoconus Progression

Progression Definition
Mastropasqua	Vazirani et al. Definition	Keratoconus Global Consensus
• Kmax increase > 1 D over a year • Change of myopia or astigmatism ≥ 3 D in 6 months • Kmean change ≥ 1.5 D in 3 consecutive topographies over 6 months • Decrease in corneal thickness of ≥ 5% in 6 months	• Kmax ≥ 1 D increase • Kmax− Kmin ≥ 1 D increase • Kmean ≥ 0.75 D increase • Pachymetry ≥ 2% decrease in central corneal thickness • Corneal apex power > 1 D increase • Spherical equivalent > 0.5 D change	(At least two of the following parameters) • Steepening of the anterior corneal surface • Steepening of the posterior corneal surface • Thinning or an increase of corneal thickness change from the periphery to the thinnest point Documented over time and must be consistent.

TABLE 12.2

Cross-Linking Indications and Contraindications

CXL Indications	CXL Contraindications
• Progressive keratoconus • All ages • Combined procedures	• Corneal thickness < 400 µm * • Prior herpetic infection • Severe corneal scarring • History of inadequate wound healing • Ocular surface disease • Autoimmune disorders • Pregnancy • Breastfeeding

CXL, Cross-linking.

* Standard Dresden Protocol.

Corneal Cross-Linking Techniques Guideline

The Dresden protocol consists of epithelial removal with application of 0.1% riboflavin solution for 30 minutes followed by 30 minutes of UVA irradiation with a power of 3 mW/cm. Some authors have reported stabilization or flattening of corneal keratometries and stabilization or improvement of visual acuity after standard CXL.

Patients with progressive advanced keratoconus will usually present with thin corneas. The Dresden protocol establishes a corneal limit of 400 µm and involves the removal of epithelium followed by the instillation of iso-osmolar 0.1% riboflavin solution in 20% dextran. For thinner corneas (< 400 µm after epithelium removal) cross-linking can result in significant risk of endothelial cell damage; thus hypo-osmolar riboflavin has been proposed as an option for thin corneas, achieving a thickness increase of approximately 70 µm after 1 minute of instillation that remained stable for about 22 minutes. Hypo-osmolar riboflavin 0.1% solution was generated by diluting vitamin B2-riboflavin-5-phosphate 0.5% with physiological salt solution (sodium chloride 0.9% solution). Hypo-osmolar riboflavin solution does not contain dextran. It is known that de-epithelialized corneas can swell up to two times their normal thickness when irrigated with a hypo-osmolar solution; thus this method has been used in CXL. Corneas are irrigated with hypo-osmolar riboflavin until the corneal thickness reaches 400 µm. Another proposed option for thin corneas is to perform CXL with custom pachymetry-guided epithelial debridement, leaving epithelium on the thinnest area, but further research is needed to prove its safety and efficacy. A viable option for thin corneas is the use of a 90-µm soft contact lens immersed in iso-osmolar 0.1% riboflavin in dextran for 30 minutes before applying it on the de-epithelialized cornea. The advantage of this method is that it is not dependent on corneal swelling and will not cause endothelial damage; even though surface irradiance is reduced about 40% to 50% and oxygen diffusion may be decreased by the contact lens. Accelerated CXL has been used in thin corneas without endothelial loss;for better results, the use of pulsed CXL has been shown to have a higher effect owing to optimization of oxygen availability.

Photrexa (Avedro) formulations combined with the KXL device (Avedro) have been approved by the US Food and Drug Administration (FDA). This is an epi-off CXL, and either one of two riboflavin solutions: Photrexa (riboflavin 5′-phosphate ophthalmic solution 0.146%) and Photrexa Viscous (riboflavin 5′-phosphate in 20% dextran ophthalmic solution 0.146%).

Clinical Evaluation

Preoperative evaluation for CXL patients should include UCVA, biomicroscopy (emphasis on ocular surface integrity and severe corneal scarring), manifest refraction (actual and previous), topography (actual and previous), BCVA, intraocular pressure, and corneal thickness.

Topography Evaluation

One of the most critical preoperative values to measure is corneal thickness, either by corneal tomography or ultrasound pachymetry. This parameter indicates whether CXL is a suitable option. Additionally, keratometric values and different corneal indices will help to assess surgery success during follow-up.

Prognostic Factors

It has been demonstrated that eccentric cones are associated with higher keratometric values 1 year after CXL treatment. Patients with lower preoperative visual acuity had a greater improvement in visual acuity after CXL treatment.

It has been postulated that steeper corneas would be flatter after CXL, rarely exceeding 2 diopters (D), but it is also known that corneas steeper than 58 D would have greater risk of progression especially if the cone is eccentric; and an increased risk of decreased vision with K > 55 D.

Patients should be advised that the treatment failure rate ranges from 8.1% to 33.3% (continued progression with Kmax readings increasing more than 1 D). It is important to explain that, in most cases, CXL by its own is not a refractive procedure. However, the earlier the treatment is done, the better results for the patient because it is a procedure that prevents ectasia complications rather than fixing them.

Intracorneal Ring Segments

ICRS implantation is considered a minimally invasive and reversible surgical procedure. Its main goals are to: (1) flatten and (2) regularize the cornea, decreasing low and high order aberrations, (3) improve visual acuity, and (4) delay, or eventually prevent, a corneal keratoplasty.

The Global Consensus on Keratoconus and Ectatic Diseases has recommended that surgical treatment of ectatic disorders should be considered when patients are not fully satisfied with nonsurgical treatments. General guidelines that apply to the effect of ICRS implantation were recently reviewed and described by Giacomin et al. The ICRSs effect correlates directly to its thickness and inversely to its distance to the visual axis or optical zone.

Prognostic Factors

In one study patients with poorer preoperative visual acuity achieve the greatest benefit from ICRS implantation. An uncorrected distance visual acuity (UDVA) of 20/70 or worse had a better prognosis.

Disease severity is an important factor to be considered when contemplating the use of ICRS. Some of the parameters studied as predictors of ICRS’s effect is the preoperative astigmatism in advance keratoconus, as astigmatic magnitude increases predictability of correction decreases. On the other hand, a greater reduction in spherical equivalent or keratometry has been described in patients with more advance stages of keratoconus.

Refraction, corneal topographic pattern, the preoperative aberrometry data, and the preoperative corrected distance visual acuity (CDVA) have shown to be significant predictive factors for planning of a ICRS implantation.

Patients with keratoconus who must benefit from ICRS implantation have a moderate stage of the ectatic disease. Unpredictability of this procedure remains a concern for low grade of keratoconus.

Peña-Garcia et al. proposed a nomogram for initial stages of the disease, mainly grade II of keratoconus. It takes into account only the refractive astigmatism, excluding corneal astigmatism and internal astigmatism. Their study demonstrated that a favorable outcome would be reached when the refractive and keratometric axis are perfectly aligned, and the internal astigmatism is low.

It is clear among experts that ICRS implantation has a lower predictability when compared to photorefractive procedures.

Different ICRS parameter must be taken into consideration for its selection, longer arc lengths are suitable for nipple or central cones, whereas shorter arc lengths are preferred in astigmatic cones. Thicker rings are indicated when a greater effect is desired. In thinner corneas, thinner segments are required to decrease the risk of extrusion.

Other studies have analyzed the efficacy of the femtosecond laser to dissect the ring channel; it did not reveal any significant difference when compared with a mechanical spreader regarding uncorrected distance visual acuity, CDVA, SE, maximum keratometry value, surface irregularity, or surface asymmetry indices. These studies have also shown that the femtosecond laser method produces fewer and less severe complications than the mechanical one.

Refractive Evaluation

Preoperative assessment includes uncorrected distance visual acuity (UCDVA), best-corrected distance visual acuity (BCDVA), pupil measurement slit-lamp examination, dilated fundus examination, topography, optical pachymetry, and keratometries. A manifest refractive measurement should be done whenever possible, as well as cycloplegic refraction.

Corneal Tomography/Topography Evaluation

Ectasia patterns based on corneal topography and tomography maps, thickness evaluation through a pachymetry map, and ectasia distribution are necessary to determine the ICRS type, number, thickness, asymmetry, arc of length, depth of implantation, and site of incision. Topographic maps will show the steeper half of the cone (frequently temporal-inferior), where the thicker segment is usually placed asymmetrically to achieve a maximum flattening effect. The thinner segment will be placed in the opposite half of the cornea.