EFFICACY OF CORNEAL COLLAGEN CROSSLINKING WITH RIBOFLAVIN AND ULTRAVIOLET-A IN PROGRESSIVE KERATOCONUS. Ophthalmology

400 microns after removal of epithelium. While patients with pachymetry reading less than or equal to 400 microns, central and paracentral scars either in the epithelium or in the corneal stroma, collagen vascular diseases, Active ophthalmic inammation, History of herpetic keratitis, Current corneal infection, Pregnancy and lactation, Severe dry eye, Autoimmune diseases and patients with previous ocular surgeries were excluded. Demographic data of patients was collected including name, age, sex, occupation and personal details. Detailed history of patients complaining of diminution of vision was taken including duration and relevant past history. Secondary causes of diminution of vision were identied. A baseline ophthalmic examination was performed on all eyes, which included slit lamp biomicroscopy, ultrasonic corneal pachymetry, and simultaneous measurement of corneal tomography and Scheimpug camera-based corneal topography. Snellen visual acuity was converted to the corresponding logarithm of the minimum angle of resolution (logMAR) value using standard conversion tables for the purpose of statistical analysis. All ABSTRACT PURPOSE- To evaluate outcomes of collagen crosslinking in patients having progressive keratoconus. METHODS- A prospective study was done in eyes that underwent corneal collagen crosslinking for treatment of progressive keratoconus. This study was performed after approval from Institutional Ethics Committee and informed consent was obtained from all the patients. Data was analysed with the help of JASP 0.8.3.1 and MS-Excel 2013. RESULT- The mean age was 20.94 ± 2.04 years. 21 (63.63%) were males, 12 (36.36 %) were females. The mean uncorrected visual acuity (UCVA) pre-operative and post-operative at 6 months were 0.64 ± 0.37 and 0.53 ± 0.31 (logMAR) respectively (p value 0.03). Mean spherical equivalent pre-operatively and post-operatively at 6 months were -2.85 ± 2.14 and -2.38 ± 1.70 respectively (p < 0.001). Mean keratometry (Mean K) pre- operative and post-operative were 49.85 ± 4.10 Dioptres (D) and 49.22 ± 4.09 D respectively (p = 0.0007). CONCLUSION- Corneal collagen crosslinking with UV-A and riboavin is a safe and effective method for halting the deterioration of progressive keratoconus.


INTRODUCTION
Keratoconus is a non-inammatory, degenerative disorder disting uished by paracentral corneal thinning and secondary ectasia resulting in irregular astigmatism, severe myopia which lead to progressive 1 impairment of vision.
Progressive keratoconus is dened as-one of the following changes over 12 months-Ÿ An increase of 1.00 diopter (D) or more in the steepest K value, 2 Ÿ An increase of 1.00 diopter or more in manifest cylinder. The prevalence of keratoconus varies considerably according to ethnic and regional factors, ranging from 50 and 600 in 1, 00,000 individuals in the general population; its incidence rate is 1 to 2 in 1,00,000 3 individual. The onset is typically at puberty with progression of 4,5 disease for 10-20 years when it tends to stabilize.
Its etiology is not understood and includes genetic, biochemical and physical factors. It usually appears as an isolate condition but has been associated with number of ocular and systemic disorders including vernal disease, retinitis pigmentosa, atopy, blue sclera, magnesium deciency, Down's syndrome, connective tissue disorders like Marfans syndrome, Ehler Danlos syndrome, osteogenesis imperfecta and pseudoxanthoma elasticum.
Management of keratoconus depends on their severity and the extent of irregular astigmatism. Mild cases are correctible with spectacles and soft toric contact lenses. However, with the progressive disease, the cornea becomes more irregular and rigid gas permeable lenses are 3 required. In 15-20 percent of keratoconic patients, surgery, typically penetrating keratoplasty becomes necessary as a result of contact lens 5 intolerance, corneal scarring and thinning. Corneal collagen crosslinking enhances the mechanical strength and biochemical stability of the cornea and is the only treatment to date that addresses 5 the pathophysiology of Keratoconus. Crosslinking is performed by using UVA at 370nm and the photosensitizer riboavin stiffening the collagen matrix of the cornea. Riboavin, administered topically to deepithelialized corneas, serves as photosensitizer that is activated by UVA light. The light induced production of oxygen radicals lead to the 3 development of strong chemical bonds between collagen brils. With the aid of this new approach, stromal ber photopolymerization enhances the corneal integrity and mechanical strength. Therefore, it may be considered as halting keratectasia progression during the progressive phase of keratoconus.
The principal goals of such therapy are to increase corneal rigidity, stabilize its refractive and biomechanical properties and thus improve 4 vision. In contrast, modern therapies such as rigid contact lenses, intracorneal rings, photorefractive keratectomy or epikeratoplasty can be used only to correct refractive errors of the disease rather than to stop the keratoconus progression.
The aim of this study was to evaluate outcomes of collagen crossli nking in patients having progressive keratoconus.

METHODOLOGY
It was a prospective, hospital based study in 39 eyes that underwent corneal collagen crosslinking for treatment of progressive keratoconus in Mahatme Eye Bank and Eye hospital, Nagpur from August 2017 to October 2018. This study was performed after approval from Institutional ethics committee and considering the principles of the Declaration of Helsinki. Informed consent was obtained from all the patients.
Inclusion criteria were Age -more than 18 years of age, progressive keratoconus with one of the changes over 12 months such as an increase of 1.00 diopter (D) or more in the steepest K value or an increase of 1.00 diopter or more in manifest cylinder, minimal central corneal thickness not less than 400 microns after removal of epithelium. While patients with pachymetry reading less than or equal to 400 microns, central and paracentral scars either in the epithelium or in the corneal stroma, collagen vascular diseases, Active ophthalmic inammation, History of herpetic keratitis, Current corneal infection, Pregnancy and lactation, Severe dry eye, Autoimmune diseases and patients with previous ocular surgeries were excluded.
Demographic data of patients was collected including name, age, sex, occupation and personal details. Detailed history of patients complaining of diminution of vision was taken including duration and relevant past history. Secondary causes of diminution of vision were identied.
A baseline ophthalmic examination was performed on all eyes, which included slit lamp biomicroscopy, ultrasonic corneal pachymetry, and simultaneous measurement of corneal tomography and Scheimpug camera-based corneal topography.
Snellen visual acuity was converted to the corresponding logarithm of the minimum angle of resolution (logMAR) value using standard conversion tables for the purpose of statistical analysis. All International Journal of Scientific Research measurements was obtained by an experienced operator using the same machines and procedures.
Uncorrected visual acuity, Best corrected visual acuity, Spherical equivalent, mean keratometry reading (from topography) and Central corneal thickness were evaluated.
Patients were followed for a period of 6 months.
Collagen crosslinking was performed under topical anaesthesia (paracaine) before procedure. Topical steroid (Prednisolone acetate 1% eye drops) and antibiotic (moxioxacin 0.5% eye drops) four times daily for one week; steroid tapered to three times/day for the next week and then two times/day for the next 2 weeks and lacrimal substitutes (preservative-free articial tears) four times daily for 4-6 weeks were the post-operative treatment given.
Data analysis was done with the help of JASP 0.8.3.1 and MS-Excel 2013. Descriptive statistics such as mean, standard deviation (SD), 95% condence intervals (CI) were analyzed. Wilcox Signed Rank test was used. P value less than 0.05 was considered signicant.

RESULT
In this study, age of the patients were ranging from 18 to 26 years with mean age being 20 ± 2.06 (SD) years. 63.63% of the total cases were males and 36.36% were females.

Table 1: Age distribution among study cases
The above table 1 shows that 36.36% of patients were belonged to 19 years of age followed by 21% of 20 years of age.
Mean central corneal thickness was 440.54 ± 11.97 and post-operative mean central corneal thickness at 6 months was 436.00 ± 12.73

DISCUSSION
In this study, we compared the efcacy in the form of topographic (Mean keratometry), refractive (spherical equivalent) and visual outcomes (uncorrected and best corrected visual acuity). Patients were followed upto 6 months and results were then analysed. We had a total of 39 eyes of 33 patients.
In our study, we noted that patients were of age 18 to 26 years, mean age was 20.94 ± 2.04 years. 36.36% of patients belonged to 19 years of age followed by 21.21% of 20 years of age. The study done by Tiveron Jr et al and Agrawal et al, reported that the mean age of the patients 6,7 were 19.9 ± 5.61 years and 16.9 ± 3.5 years respectively. Our study was in concordance with these studies. This concluded that keratoconus occurs in younger population.
The present study results depicted the mean pre-operative and postoperative best corrected visual acuity (BCVA) at 6 months were 0.31 ± 0.29 and 0.19 ± 0.20 (logMAR) respectively and were found to be statistically signicant (p value<0.001). Amongst 39 eyes, one line improvement was evident in 7 eyes (17.94%); two lines improvement in 10 eyes (25.64%); three lines improvement in 2 eyes (5.13%). Also, we found that in 19 eyes (48.72%) BCVA remained stable and one line worsened in one eye (2.56%).
Our study results were found to be congruent and comparable with the In this study, out of 39 eyes, spherical equivalent (SE) of 19 eyes remained stable (48.71 %) and decreased in 18 eyes (46.15%). Mean spherical equivalent pre-operatively and post-operatively at 6 months were -2. 85 ± 2.14 and -2.38 ± 1.70 respectively (p < 0.001). A study conducted by Vinciguerra et al in 2009, noted mean spherical equivalent pre-operative and post-operative was -3.63 ± 3.45 and 2.06 ± 2.21 respectively; the difference between them was statistically 9 signicant (p = 0.03).
O Brart et al, evaluated 30 eyes in 2013. They noted that mean spherical equivalent pre-operative and post-operative was -1.61 ± 1.97 and 0.79 ± 1.7 respectively. The difference between two was 11 statistically signicant (p value < 0.001). Our study results were co- 9,11 relating with the results of Vinciguerra et al and O Brart et al. We thus concluded that there is signicant improvement in refractive outcome (spherical equivalent).
In this study, Mean keratometry (mean K) pre-operative and postoperative were 49.85 ± 4.10 Diopters (D) and 49.22 ± 4.09 D respectively (p = 0.0007). We also noted that, there were 34 stable eyes (87.17 %) post corneal collagen crosslinking and remained in the same preoperative mean K class. Mean K decreased in about 4 eyes (10.25 %). These results demonstrate a attening effect of crosslinking on keratoconic eyes. A study by Vinciguerra et al, found that mean K decreased from 50.37 D pre-operative to 49.02 D post-operative which 12 when compared were statistically signicant (p= 0.03). In a study conducted by O Brart et al, mean K pre-operative and post-operative 11 were 46.44± 3.4 D and 45.6 ± 3.3D respectively. These when compared were statistically signicant (p value < 0.001). Ivarsen et al in 2013, noted that mean K pre-operative and post-operative were 61.2 ± 3.7 D and 59.1 ± 3.7 D and were found statistically signicant when 13 compared with each other. Our results were comparable with the 11-studies conducted by O'Brart et al, Vinciguerra et al and Ivarsen et al. 13 We inferred that there is a signicant reduction of mean keratometry at 6 post-operative months.
Preoperative mean central corneal thickness was 440.54 ± 11.97 microns and post-operative mean central corneal thickness at 6 months was 436.00 ± 12.73 microns. The results when compared were found to be statistically signicant (p< 0.05).
In a study conducted by Vinceguerra et al, found that the mean CCT