This study aims to compare the ocular health and visual quality of corneal rigid gas permeable lenses (CRGPL) and scleral rigid gas permeable lenses (SRGPL) for patients with keratoconus in a crossover clinical trial. The study will analyze subjective and objective outcomes, including best corrected visual acuity, contrast sensitivity, higher-order aberrations and subjective perception of visual function and comfort. It will also investigate the impact of both lens types on the health of the ocular surface, including evaluation of corneal, conjunctival, and scleral tissues, and tear film. Only one randomized controlled trial has compared the effect of CRGPL and SRGPL wear for patients with an ectatic corneal disorder. With the increasing popularity of SRGPL, examining the differences in efficacy, safety, and patient-reported outcomes between the two types of lenses is increasingly relevant.

A comparison of ocular health and visual quality with corneal and scleral rigid gas permeable lenses in keratoconus patients

1. Introduction

1.1 Purpose: Keratoconus is an ocular disease, causing progressive thinning and steepening of the cornea, which results in irregular astigmatism and reduced visual quality. Irregular astigmatism induced by an irregular anterior cornea can effectively be corrected with rigid gas permeable (RGP) lenses. The purpose of this study is to compare subjective and objective outcomes from corneal rigid gas permeable lens (CRGPL) and scleral rigid gas permeable lens (SRGPL) wear in patients with keratoconus.

The following three aims will be pursued during a randomized clinical trial (RCT)

1. To compare the subjective perception of visual function (SPVF), subjective perception of comfort (SPC) and objective measures for visual quality, including best corrected visual acuity (BCVA) and contrast sensitivity (CS), between CRGPL and SRGPL wear, for patients diagnosed with keratoconus.
2. To analyze the effect of CRGPL and SRGPL on higher order aberrations (HOA) for patients with keratoconus.
3. To investigate the impact of CRGPL and SRGPL wear on the ocular surface, including analysis of the corneal, conjunctival, and scleral tissue, as well as tear film analysis, for patients with keratoconus.

1.2 Hypothesis

1. SPVF and SPC will be significantly better for SRGPL wear compared to CRGPL wear, but the difference in clinical findings for visual quality will be insignificant.
2. The difference in reduction of HOA between CRGPL and SRGPL wear will be insignificant, but the overall HOA for both interventions will decrease significantly compared to baseline.
3. Significant variation in health of the anterior eye will be observed for CRGPL and SRGPL wear. SRGPL wear will more frequently exhibit adverse effects at the conjunctival and scleral tissue, whereas the corneal tissue will show more complications with CRGPL wear. Symptoms and clinical findings related to dry eye disease (DED) will be significantly superior with SRGPL wear.

2. Background

2.1 RGP lenses Fitting RGP lenses for patients with an irregular cornea, such as keratoconus, is a common optical rehabilitating treatment. Due to elevated HOA in patients with keratoconus, RGP lenses have the distinct advantage of significantly improving the visual quality through a reduction in aberrations from the anterior cornea with the tear lens between the cornea and the lens. Both CRGPL and SRGPL wear have been shown to potentially delay the need for corneal transplants in patients with keratoconus.

A CRGPL is designed to fit within the corneal diameter whereas the SRGPL is produced in a larger diameter, and designed with a bearing that rests solely on the conjunctival tissue. CRGPL fitting for keratoconus has traditionally followed one of three different design objectives. Apical clearance, apical touch, or three-point touch. The three-point touch method has shown better fitting success compared to the apical touch, which has the added risk of potentially inducing corneal scarring. The SRGPL has the unique advantage of being fitted without having any contact with the irregular cornea of patients with keratoconus and is increasingly useful in more advanced cases.

The effect on visual quality from CRGPL and SRGPL wear on patients with an ectatic corneal disorder has been compared in only one RCT with a study population consisting of 34 patients successfully fitted with CRGPL. Patients were fitted with both CRGPL and SRGPL designs in a crossover study. The difference in BCVA and CS between the two lens types was not statistically significant. This study differs by analyzing a larger variety of parameters related to ocular health, the tear film and higher order aberrations. The study population is also expected to be more homogeneous, since it will consist solely of patients with keratoconus and with no prior history of RGP lens wear, to minimize the risk of bias.

2.2 Higher order aberrations The ocular structures responsible for the refractive properties of the eye are the cornea and the crystalline lens. The shape and regularity of these structures influence how much the wavefront will deviate from an ideal wavefront. This deviation is also known as wavefront aberration. Wavefront aberrations are commonly categorized as lower-order aberrations (LOA) or higher-order aberrations (HOA) and can be described using the Zernike polynomials. Some HOA explained through Zernike polynomials, such as coma and trefoil, are most often seen in irregular corneas, and are usually managed with RGP lenses. Wavefront aberrations are quantifiable using an aberrometer, making it possible to compare the effect of different lens designs on the amount of residual HOA.

2.3 Complications from RGP lens wear Contact lens wear, regardless of modality, will potentially cause complications. For CRGPL most complications are located at the cornea, palpebrae, and tear film. Complications from CRGPL wear include 3 and 9 o'clock corneal staining, mechanical corneal staining, and vascularized limbal keratitis. Studies have also shown a potential risk of developing ptosis from CRGPL wear.

SRGPL wear potentially induces corneal oedema and conjunctival prolapse. From multiple smaller studies patients with keratoconus, wearing a modern SRGPL, exhibited an average corneal oedema of ~2%. Blurred vision from tear reservoir debris has also been observed in patients wearing a SRGPL. This phenomenon is known as midday fogging and has been estimated to occur in about 26-46% of SRGPL wearers.

3. Materials and methods The study population will consist of patients with keratoconus referred to the Department of Ophthalmology at Aarhus University Hospital.

Suitable subjects will be invited to participate in the study, and randomized to start with one of two interventions, CRGPL or SRGPL wear in a crossover clinical trial. Study subjects must comply with the following inclusion criteria: Keratoconus, best spectacle corrected visual acuity >0.00 log of minimum angle of resolution (logMAR) and age between 18 to 40. The exclusion criteria for this study are: K-max >60D, RGP lens wear at baseline and ocular surface disease, verified through examination of the ocular surface and patient history.

The study involves analysis of multiple different outcomes but to determine an appropriate sample size, BCVA using logMAR has been chosen as the primary outcome and therefore the sample size is calculated per findings related to that.

The mean logMAR for patients with keratoconus wearing a CRGPL from the studies used is 0.08 (0.10), and 0.18 (0.17) for SRGPL wear. Sample size calculations with α = 0.05 and β = 0.90 yield a required study population of 35 subjects, to detect a difference of 0.10 logMAR. To account for potential drop-out this study will aim to include 50 subjects.

Aim 1: To investigate the visual quality of patients with keratoconus during both CRGPL and SRGPL wear, BCVA using ETDRS standard charts, translated to logMAR units, and CS measured with the Pelli Robson chart, will be obtained. Furthermore, the SPVF will be analyzed using the validated Visual Function Questionnaire (VEQ-25), translated to a Danish validated version. The SPC will be quantified with a questionnaire developed specifically for this study. For fitting of contact lenses, corneal shape will be measured with the Pentacam HR tomography (Oculus, Switzerland) device and the Heidelberg SPECTRALIS OCT device (Heidelberg Engineering, UK).

Aim 2: The effect of CRGPL and SRGPL on the amount of HOA during lens wear will be measured using Hartmann Shack aberrometry with the Visual Adaptive Optics simulator (VAO) (Voptica, Spain).

Aim 3: During this part of the study the ocular health will be monitored before, during, and after CRGPL and SRGPL wear. The ocular health examination will include standardized grading of conjunctival and limbal hyperaemia, corneal neovascularization, corneal oedema, and staining of the ocular surface. The examination will be quantified using the Efron Grading scale, and documented with slit lamp photography. Corneal epithelial thickness and corneal tomography will also be examined before and after each intervention. Symptoms and clinical findings related to dry eye disease (DED) will be evaluated using the validated symptom survey "Ocular Surface Disease Index" (OSDI), translated to Danish and measured with break-up time (BUT).

4. Ethical considerations Since contact lenses are classified as medical devices, approval has been obtained from the Danish Medical Research Ethics Committees. When patients are invited to participate in the study, they will receive written information on the purpose of the study including an explanation of risks and benefits of the interventions. To participate an informed consent form must be obtained. The study will be conducted in agreement with the declaration of Helsinki, and patient data will be stored in agreement with the relevant Danish law. Since the intervention is to be administered and cared for by the patients at their residence, proper instruction of use will be delivered both in writing and verbally in the clinic.

5. Perspectives The prevalence of keratoconus shows substantial variation globally, with epidemiological studies estimating it between 0.2 and 4,790 per 100,000 persons. In Denmark the prevalence was estimated, by Bak-Nielsen et al (2019), to 40 per 100,000 persons. Research indicate that the incidence of patients with keratoconus has increased significantly in Denmark over the last 30 years. Nielsen et al (2007) estimated the incidence to 1.3 per 100,000 person-year based on data from 1995 to 2005. Bak-Nielsen et al (2019) estimated the same incidence to 3.8 per 100,000 person-year based on data from 2011 to 2015. The authors attribute a large portion of the increase in incidence to the introduction of CXL, which has changed the referral pattern. Treatment with CXL reduce the need for corneal transplantation, improves visual quality and reduces cone progression. Patients with keratoconus post CXL, generally still require RGP lenses as they remain the best option for improving visual quality.

The "International Contact Lens Prescribing"-reports investigate global contact lens prescribing trends. In 2013 scleral lens fits accounted for ~6% of all RGP lens fits reported, that increased to 22% in 2023. In Denmark there is a reported increase in RGP lens fits of total lens fits. In 2013 RGP lens fits accounted for 8% of all lens fits reported, this increased to 18% in 2023. With the increasing popularity of scleral lenses and the growing number of RGP lens fits reported in Denmark, research examining the differences in efficacy, safety and patient reported outcomes between the two types of lenses are increasingly relevant.

Inclusion Criteria:

• Keratoconus, best spectacle corrected visual acuity >0.00 log of minimum angle of resolution (logMAR) and age between 18 to 40

Exclusion Criteria:

• K-max >60D, RGP lens wear at baseline and ocular surface disease, verified through examination of the ocular surface and patient history