Corneal Cross Linkage in Patients with Unstable Keratoconus: Comparative Analysis of Visual Outcome after 1 Year Follow-up

Objective: To report on 1-year postoperative visual outcome with the corneal cross linkage for unstable keratoconus
Material and methods: Thirty eyes of 15 patients with unstable keratoconus and myopia between 0.00 and 17.00 DS and
astigmatism between 1:00 and 8:00 DS were analyzed in this prospective interventional study. The visual outcome was
analyzed on the best possible refraction and topographic readings preoperative and post operative.
Results: At 1-year follow-up, 45% had 20/20 vision or better and 100% had 20/40 or better uncorrected visual acuity
(UCVA). Vector analysis of refractive astigmatism shows that the surgically induced astigmatism (SIA) (3.20 1.46 D) was
not significantly different from the target induced astigmatism (TIA) (3.14, 1.42 D) (p=0.620). At 1 years postoperatively,
none of the eyes showed a decrease in UCVA, in contrast to 24 eyes in which UCVA was increased by 1 lines, with
contrast sensitivity and improvement in total aberrations and MTF value at 5 per degree (*p=0.004) after CXL surgery. The
cumulative 1- year corneal endothelial cell loss was 5%. No patients reported dissatisfaction. At the end of followup,
the vault was 658 + 54.33m (range, 500–711) and the intraocular pressure was 11.7 + 2.08 mm Hg. Occurrences of glare
and night-driving troubles diminished after CXL surgery.
Conclusion: The results of this prospective interventional study support corneal cross linkage for unstable keratoconus.
Key Words: Corneal cross linkage, keratoconus,


Keratoconus is a disorder of the cornea which results in progressive thinning of the cornea that induces irregular astigmatism, resulting in impairment of vision. 1 keratoconus is derived from Greek words kerato (cornea) and konos (cone). It usually affects both the eyes and may result in corneal perforation of corneal scaring.2 Keratocnus is usaly diagnosed in second and third decade of life and affects quality of life of young adults. 3 Keratoconus affects about 1 in 2000 people.1,2 Despite considerable research, the cause of keratoconus remains unclear. 4Several sources suggest that keratoconus likely arises from a number of different factors: genetic, environmental, cellular, any of which may form the trigger for the onset of the disease.5 However, the exact mechanism by which it manifests in terms of progression, genetic heterogeneity and phenotypic diversity is not known, thereby resulting in a series of diverse diagnostic and treatment methods.6,7 In early stages of keratoconus, glasses or soft contact lenses can suffice to correct for the mild astigmatism.

1.HOD.,PICO, Hayatabad Medical Complex Peshawar2. Lecturer
Optometry PEF College Peshawar3. Lecturer Optometry, PEF
College Peshawar4. Deputy Director PICO, Hayatabad Medical
Complex Peshawar5. Assistant Professor PICO, Hayatabad Medical
Complex Peshawar

Correspondence. Dr. Junaid Faisal Wazir Email: junpak2@hotmail.
com Contact: 00923339105154 House No 296. Street 5, E4, Phase
7, Hayatabad, Peshawar

Received: May’2019 Accepted: June’2019

Prospective interventional study supports corneal cross linkage for unstable keratoconus.

As the condition progresses, these may no longer provide the person with a satisfactory degree of visual acuity, and most practitioners will move to manage the condition with rigid contact lenses, known as rigid gas permeable lenses (RGP) lenses.8 Between 11% and 27% of cases of keratoconus, it will progress to a point where vision correction is no longer possible, thinning of the cornea becomes excessive, or scarring as a result of contact lens wear. 9, 10, 11 Surgical treatment in form of keratoplasy (Corneal transplantation) is then required for such patients. Another technique which is called corneal rings implants are alternative of keratoplasty which is performed by the insertion of intrastromal corneal ring segments. A small incision is made in the periphery of the cornea and two thin arcs of polymeth-yl methacrylate are slid between the layers of the stroma on either side of the pupil before the incision is closed by a suture. 12 The new and innovative technique which is still developing in the world is corneal cross linkage it aims to strengthen the cornea, however, according to a 2015 Cochrane review, there is insufficient evidence to determine if it is useful in keratoconus.13 In 2016, the American food and drug administration approved riboflavin ophthalmic solution and CXL system for cross linking based on three 12-month clinical trials.14 METHODOLOGY: This was a prospective interventional study. Fifteen patients (30 eyes) age 15–40 years with systemic and other ocular diseases except keratoconas were included in this study and treated with corneal collagen cross linking (CXL) in 1 year follow up in hospital. These cases were selected using a non- random consecutive sampling method. Before starting the study, informed written consent was taken from every participant before study. Study approval was taken from institution ethical review committee of Pakistan Instittue of Community Ophthalmology (PICO) Peshawar. After 6 months post CXL, the refraction was declared as stable if there was a change in refraction of six subjective refractions within +0.75 D of spherical equivalent. Those patients were included whose best corrected visual acuity was 6/12, K max <53, intraocular pressure (IOP) <21mm Hg, clear cornea, normal ACD of at least 3.5 mm to the endothelium width of angle greater than 30 degree. Contact lens use was discontinued for at least 2 weeks for rigid lenses and 1 week for soft lenses before any intervention. Those patients who were mentally disabled, pregnant, lactating mothers and those who didn’t signed consent form were excluded from the study. RESULTS: A summary of patient demographics is provided in table 1.

The mean spherical error was - 5.06 +3.96 D (range: 0.00 to -18.00 D), and the cylindrical error was -3.57+1.56 D (range: -1.25 to -8.00 D). Patients at the time of surgery were aged 30.57+4.69 years (range 25–38 years). CXL was performed at the clinical investigational site in this group. Patients were followed up five times after surgery at 1 month, 2 month 3 month and 6 months and then 1, year. At year postoperatively, 82.5% of eyes were within +0.50 D, and 97.05% were within +1.0 D of attempted correction, and the mean spherical and cylindrical manifest refractions were 0.44 +0.40 D and -1.01 +0.44 D, respectively. At the end of the follow-up, the mean vault was 658 +54.33 mm (range, 500–711), and the IOP was 11.7_2.08mm Hg. All patients had a preoperative uncorrected visual acuity (UCVA) worse than 20/40 with 95% having unaided acuity limited to counting of fingers. At 1 years, postoperative UCVA was better than or equal to preoperative CDVA in 92.50% (37/40) of eyes, and UCVA was increased by >1 lines in 25 eyes in table 2.

Figure 1 A comparison of preoperative best corrected distance visual acuity and postoperative uncorrected distance visual acuity 1 year after CXL. UCVA, uncorrected visual acuity. The log MAR visual acuity under defocus curve of +2, +1, 0, -1, -2, -3 and -4 D in postoperative and preoperative periods in a noncycloplegic condition. The differences between the measurements of binocular distance corrected defocus curve in the study demonstrated significant differences in log MAR visual acuity at the defocus curve levels of +1, 0 and -1 D, but no significant difference was observed at the defocus curve level of +2, -2, -3 and -4 D.

Fig.2:Log MAR (logarithm of the minimum angle of resolution) visual acuity defocus curve of +2, +1, 0, 1, 2, 3 and 4 D in a non-cycloplegic condition in the preoperative and postoperative MTFs were estimated for six spatial frequencies (5, 10, 15, 20, 25 and 30 C/ D) from the ray-tracing aberrometer at a pupil diameter of 6 mm.

Figure 3 demonstrated a significant improvement in MTF value at 5 per degree (p=0.004). Preoperative and postoperative corneal and ocular aberrations for the current study, according to evaluation after 1year, showed significant improvement in total aberrations after CXL.

Figure 4 Total and corneal aberrations in 40 eyes with keratoconus before and after undergoing CXL surgery. *Statistically significantly different at a level of 0.05. RMS, root mean square.


This study demonstrated the visual results of CXL in unstable keratoconus with a long-term follow- up. Our observations were similar to those of other studies with respect to the supportive safety, efficacy, predictability and stability of this procedure in patients with stable keratoconus. In our study, similar to report of González- López, in which a significant improvement in UDVA and CDVA was demonstrated. 15 The visual acuity test is gradually becoming standard for evaluation of vision, as it provides only a limited amount of data inartificial conditions. The contrast sensitivity tests presented a variety of visual performance data under real conditions.16, 17 This motivated us to advance in this area of medicine. To the best of our knowledge, this is the first CXL study in patients with unstable keratoconus (not limited to mild and moderate) with a longterm follow-up that focuses on quality indexes (contrast sensitivity, MTF, curve aberrations and defocus) in January 2018. The amount of aberrations in the eye is related to factors such as age, refraction, severity of keratoconus and even techniques of evaluation.18,19 In the current study, after one year of follow-up evaluation of the aberration using the ray tracing technology, there was a significant improvement in the total aberrations after the CXL compared to the previous treatment, and the CXL for six spatial frequencies (5, 10, 15, 20, 25 and 30 c / d) of the ray tracing aberrometer with a pupil diameter of 6 mm. Improvement of MTF value to 5 per degree (* p = 0.004). A blurred asymmetric retinal image exerted by higher order aberrations in keratoconic eyes with CXL seems to compensate through mechanisms such as the neural visual system and other related components that help to improve the long-term visual experience. 21,21 The CXL is a feasible approach with less invasion in visual performance, because it does not change the curvature relationships between the anterior and posterior corneas.6 In this regard, although some approaches may show slightly better results for uncorrected visual acuity and predictability of refraction, in a study conducted by Alfonso, CXL showed reliable results similar to those of bioptics. A single procedure with CXL can avoid possible complications for a second alternative surgery.22 Some studies reported a trend towards decreased corneal transplantation for keratoconus compared to two different periods.23,24 It is a promise that seems to be related to contemporary management modalities in the early detection of keratoconus progression and treatments.25 The divorce available on the market riboflavin (more potent riboflavin with less cytotoxicity), better protocols and cross-linking techniques ‘the procedure to stop the progression of the disease’26,27 may allow the correction of visual defects in patients with keratoconus, by What, the CXL implantation becomes a perfect refractive surgical correction
technique in the future.28


The results of this prospective interventional study support corneal cross linkage for unstable keratoconus.

Hydroxychloroquine toxicity 
A 60-year-old woman presented to the ophthalmology clinic after noticing central blind spots in the visual fields of both eyes. She had a history of rheumatoid arthritis, which had been treated with hydroxychloroquine for 14 years. The retinal examination showed the pattern below.
Differential Diagnosis: Rheumatoid arthritis, Hydroxychloroquine toxicity, Age-related macular degeneration, Type 2 diabetes, Bardet-Biedl syndrome.  Curtsey: NEJM


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