Original Article

Initial Experience of Corneal Collagen Cross Linking in Progressive Keratoconus

Munira Shakir, Faiza Rameez, Shakir Zafar, Muhammad Ahsan Sulaiman

Pak J Ophthalmol 2018, Vol. 34, No. 2

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authors affiliations

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Correspondence to:

Munira Shakir

Liaquat National Hospital, Stadium Road, Karachi, Pakistan

Email: dr_munirasz@yahoo.com

Purpose: To assess the outcome of Corneal Collagen Cross-linking (CCXL) in patients with progressive Keratoconus in terms of satisfaction.

Study Design: Descriptive case series.

Place and Duration of Study: This study was conducted at Liaquat National Hospital, Karachi, Pakistan. It documents a process that is spread on one year.

Material and Methods: This prospective study is comprised of 34 patients who had bilateral Corneal Cross linking (CXL) treatment for progressive Keratoconus. Analysis was performed in terms of amount of corneal flattening (observed through topography), effect on vision (observed through Snellen’s Chart) and satisfaction of patient (assessed by filling of proforma 6 months post-operatively).

Results:. Findings of 31 cases were analyzed as 3 cases missed the follow-up. Mean age was 23.2 ± 5.5 years. 61.3% of the cases were males while 38.7% were females with respective frequency of 19 and 12. Mean post-operative BCVA on Snellen’s Chart improved on average by more than one line. Post-operative mean of change in steepest K reading was 1.29 ± 0.52D. 16.13% of the cases were happy after treatment, while 64.52% were satisfied. However, 19.35% of the cases were unhappy.

Conclusion: This study shows that CXL retards progression and generally brings satisfaction among the participants.

Keywords: Corneal Collagen Cross linking, Keratoconus, Corneal Topography.

Keratoconus is a condition characterized by corneal steepening typically inferior to central cornea with corneal thinning, induced myopia and both regular and irregular stigmatism. It is usually a bilateral condition and is non-inflammatory¹.

The onset is around puberty with slow progression until third and fourth decades of life. Many treatment options are available including conservative options such as spectacles and rigid contact lenses. Surgical options for the treatment include: intra-corneal ring segments; Phakic Intra Ocular Lens (IOL); Refractive Lens Exchange (RLE); Anterior Lamellar Keratoplasty (ALK); and Penetrating Keratoplasty (PK)^1-3.

A disturbed cross-linking within or among the collagen molecule has been observed in Keratoconus. By photo-oxidative collagen cross-linking with riboflavin and ultra violet light, additional covalent bindings between the collagen molecules is achieved which stabilizes the collagen scaffold¹.

Eberhard Spoesi and Theo Sieler developed Corneal Cross linking (CXL) procedure in late 1990s⁴. Wollensak et al⁵believed that collagen cross-linking was becoming a standard treatment for Keratoconus.

The aim of this case series is to evaluate the results of CXL in the patients with progressive Keratoconus and the index of patient satisfaction is being used as a main gauge for proving its effectiveness.

MATERIAL AND METHODS

This study documents an ongoing case series, which was conducted in Liaquat National Hospital, Karachi, Pakistan. 34 cases of more than 10 years with central corneal ectasia and having commitment to follow up of six months were included in the study. Each patient was first time assessed at day one, then after a week, then monthly for 6 months and corneal topography was repeated at 3 and 6 months. Patients filled a proforma after topography. Exclusion criteria for this study was; any patient having corneal thickness less than 400μm⁶; corneal scarring in the eye to be treated; loss to follow-up; prior history of corneal surgery.

This study was conducted after getting an informed written consent of all the participants. It was carried out under the supervision of an advisory committee.

Pre-operative complete ocular checkup was done including: Visual Acuity; Best Corrected Visual Acuity (BCVA) through Snellen’s Chart; IOP through Goldman Applanation Tonometer; Corneal Topography by Pentacam; and Pachymetry (Ultrasonic and Pentacam). Further relevant information was collected, using a proforma, on follow ups. The CXL was done as a day-care procedure under sterilized environment. The inclusion criteria for this study, which is similar to O’bart et al⁷ included; Age between 16 – 35, no prior history of ocular surgery, steepest K value between 48 D and 60 D, corneal thickness > 400 μm, patient must meet the diagnostic criteria for Keratoconus⁸, progression verified by corneal topography i.e.: Change of max. K by 1D⁹.

CBM VEGA X-linker – device that emits UV radiation at 365-370nm after proper calibration to direct 5.4 J/cm² to the cornea – was used on all the participant of this study. Pre-operative antibiotics were given after the instillation of anesthetic drops. Seiler or epi-off technique was used. A lid speculum was applied. After removing the epithelium, drops of riboflavin 0.1% (Vitamin B2) were given at 1-5 minutes for 30 minutes or until it is visible in the anterior chamber. After riboflavin absorption, the participant was exposed to the UV light which was placed closer i.e. 1-5 cm from the corneal apex. A small digital video camera was included in the Ultra-Violet A (UVA) array in order to monitor the aiming beam. Following irradiation, cornea was rinsed with chilled saline, drops of antibiotic were applied and Bandage Contact Lens (BCL) was placed.

Post-operatively, topical antibiotics, topical steroids (4 times a day), artificial tears, painkiller and oral vitamin-C were given. BCL was removed after 3-4 days. This post-operative regimen was in line with Sherif et al¹⁰.

Data were analyzed using Minitab. Mean and standard deviation (SD) were used to define the variables. Frequency and percentage were used to define variables such as satisfaction index (ordinal variable) and gender. Descriptive statistics were developed and presented in the section of Results. P-value < 0.05 was considered as significant for normality testing of data. Correlation of the two interval variables (Vision Improvement and Flattening) was further determined using Pearson Coefficient.

RESULTS

34 cases were studied for this research; however, three cases were lost for follow-up. Analysis of the remaining 31 cases, who completed the follow-up, was carried out. All cases had progressive Keratoconus, and other ectasias were excluded from this study. For corneal stabilization, pre- and post-operative topographic readings were taken as criteria. In addition, BCVA was carried out through Snellen’s Chart and was taken as another criterion. 61.3% of the cases were males while 38.7% were females with respective frequency of 19 and 12. Mean age was 23.2 ± 5.5 years.

Mean post-operative BCVA on Snellen’s Chart improved by more than one line. Specifically, the mean of change in vision improvement on Snellen’s Chart was additional 1.5 ± 0.62 lines. Post-operative mean of change in steepest K reading was 1.29 ± 0.52D as shown in Table 2. This shows improvement as the topographic findings showed lesser steepening post-operative. Normality test was applied on each variable’s distribution, which were found to be non-normal (p < 0.1); therefore, parametric statistical methods cannot be used and the scope was limited to descriptive statistics.

At 6 months post-operative, a proforma (placed as appendix) was filled for each case to gage the satisfaction. It had three options: happy, satisfied and unhappy; thus making it an ordinal variable. 16.13% of

Table 2: Post-operative description of Variables.

Variables	Mean*	SD	p-value for Normality**
Flattening	1.2903	0.5211	< 0.006
Vision Improvement	1.5145	0.6151	< 0.005

*Mean: for flattening read’ mean decrease in steepening’, and; for vision improvement read’ mean additional lines on Snellen’s Chart’

**Anderson-Darling Normality Test was used. As the p-values are lower than 0.1 significance level, the data do not follow the normal distribution

Fig. 1: Satisfaction Response (n = 31).

the cases were happy after treatment, while 64.52% were satisfied. However, 19.35% of the cases were unhappy, as shown in Figure-1. None of the cases developed any complications.

DISCUSSION

We have found a significant flattening in the steepest K value in all the patients similar to the results of Wollensak et al⁵ in whose study the decrease of mean Keratometer value was by 2.01 D.

As compared to other therapeutic measures used for the treatment of Keratoconus such as: intra-corneal ring^1,11; and epi-keratoplasty¹; Hovkimyan et al¹², showed that CXL can be regarded as a useful approach to reduce number of keratoplasties. Wollensak et al¹³, in their study showed that mechanical rigidity increases in porcine corneas, while they reported greater increase in human corneas. Figure-2 visually describes the mean flattening and mean vision improvements in our cases. Both distributions were found to be uni-modal and negatively skewed (as shown by the box plots as well). Furthermore, figure-3 presents the scatter plot developed between these two interval variables. It manifests a marginal positive correlation, which can be testified by the value of 0.779 of Pearson’s Correlation Coefficient.

The findings of our study are in agreement with several earlier studies^4,5,14-16 that proved the significant improvement in visual acuity and maximum keratometry as well as retarding progression after CXL. However, our study further takes into account the satisfaction of the patients who went through the procedure. This was carried out using a designed proforma.

Wolensak et al.¹⁷ in their study showed that riboflavin/UVA treatment is safe for endothelium only when the dose is below 0.65 J/cm² and cornea should not be less than 400 μm thick. Adverse