Teuta Haveri, M.D.1,Sulejman Zhugli, M.D.2, Prof, Mimoza Meco, M.D.1,Eliziana Petrela M.D., Prof3

1 Eye Clinic American Hospital No.1 Tirana, Albania
2 Faculty of Medicine, Ophthalmology Department, Tirana
3 Department of Statistics, Faculty of Public Health, Hospital University Center, Tirana

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Keratoconus is a non-inflammatory degenerative disease of the cornea, which affects mostly young people from 14 – 30 years old (1). Usually it is a progressive situation, which leads to steepening and thinning of the inferior part of the cornea (2) and causing progressive loss of vision (3). These young patients, very exigent for their visual acuity, are always changing their correction (glasses or contact lenses) but not feeling comfortable with them. Extreme advancement of the keratoconus can cause extreme thinning of the cornea and risk of perforation. To avoid this devastating complication, in advanced stage keratoconus, corneal transplant is required to save the eye and the vision. It is already known that hot weather and sun is an environmental factor contributing in high incidence of keratoconus (4,5,6,7). Albania, as a Mediterranean country, offering this climate, has a relatively high incidence of keratoconus. Still not having exact statistical data for keratoconus incidence in Albania, we diagnose almost every week young patients with keratoconus which comparing to our population of 3 million habitants, shows a non-negligible incidence of the disease. Also, it is not very rare to diagnose younger children with keratoconus (8), having the youngest one diagnosed with 3-4th stage of keratoconus at 10 years old. It is not very rare also to find adults, after 35 years old, showing clear evidence of progressive keratoconus. Another fact that should be mentioned is the finding of an increased number of children 5-10 years old with high astigmatisms 4-5 diopters or more, with corneal thickness less than 500 µm, which can develop to keratoconus later. These general considerations are mentioned to underline the importance of keratoconus disease in our country and therefore showing the importance of early diagnosis and treatment with cross-linking. Nowadays, cross-linking is the only procedure used to halt the natural progression of keratoconus, Spoerl et al. were the first to report its use on stabilizing the cornea (9). After that, a great number of clinical studies supported its efficacy in halting the progression of keratoconus. Its simplicity in application and its low cost makes this treatment easily applicable. In Albania, cross-linking procedure is applying since 2009. In this paper we would like to present our results of the follow-up of patients underwent cross-linking procedure.

Patients and Methods

81 eyes of 75 patients with progressive keratoconus were included in the study. Average age was 23.5 +/- 5.2 years (the youngest was 15 years old and the oldest 38 years old). Altogether 42.3% (32 patients) were
female and 57.3% (43 patients) were male. The diagnosis of progressive keratoconus was based on:

  1. History of the patients, astigmatismus and/or myopia, frequently changing the refraction, young age.
  2. Objective examination: high keratometry values above 47 diopters in autorefractometer measurement.
  3. Slit lamp examination: presence of Fleischer ring on the cornea.
  4. Lens, retina and optic nerve examination to rule out any other accompanying pathology.
  5. Evaluation of corneal topography with Pentacam (Oculus HR) which establishes the diagnosis and keratoconus stage according to Krumeich classification.

Cross-linking technique. Patients were treated with epithelium off technique, according to Dresden Protocol.

  1. Sol. proparacaine 0.5% for 4 times on the cornea.
  2. Removal of corneal epithelium (6-8 mm diameter).
  3. 30 minutes of riboflavin administration (1 drop every 2 minutes).
  4. UVA light is applied for 30 minutes (adding also riboflavin drop every 2 minutes).
  5. Bandage soft contact lens is applied for 3-5 days until reepithelization process occurs.
  6. Antibiotic and anti-inflammatory eye drops (sol. ciprofloxacinum ophthalmic and sol. diclofenac ophthalmic) and artificial tear were given every 4 hours as the post treatment.

Postoperative assessments. Patients were examined regularly after 1 week, 1 month, 3 months, 6 months, 1 year, 2 years and 3 years after cross-linking treatment. Every time uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) were measured using Snellen chart. A topographic examination with the same instrument was performed (Pentacam HR, Ocu- lus) and keratometry values (flattest, steepest, maximal) and pachymetry values (central and thinnest) were recorded. Also a careful examination of the cornea was performed on slit lamp. Statistical analysis. Statistical analysis data were analyzed using the SPSS software (Statistical Package for Social Sciences 20.0). For all numerical variables central and dispersion tendencies were calculated. For variables following the normal distribution, arithmetic medium value and standard deviation were calculated. Differences between groups were calculated with student test. Correlation between variables was analyzed through coefficients of Kendal’s tau. Statistically significant differences were considered when the values of p£0.05.


The tendency of progression of parameters after crosslinking are presented in the following graphics. Each graphic presents the medium value of each parameters and its evolution through time starting with pretreatment values and the medium values 1 week after treatment and also 1, 3, 6, 12, 24 and 36 months after cross-linking treatment. The following parameters were recorded: flattest keratometry, steepest keratometry, maximal keratometry, UCVA, BCVA, central pachymetry, thinnest pachymetry. The reduction of keratometries became visible mostly after 6 months and continued even after 36 months. The most affected is maximal keratometry. Changes in visual acuity became also visible after 6 months, mostly affecting BCVA. Reduction in pachymetry values start at 12 months mostly due to the phenomenon of “corneal shrinking”. The changes are presented in the tables and figures.


The main parameter which define the topographic corneal shape is the radius of corneal curvature. Generally 2 of them, perpendicular to each-other, are used to topographically characterize a certain cornea (the flattest and steepest keratometry). Another keratometry value, corresponding to the apex of the cone or the point of maximal corneal elevation is recorded in Pentacam examination referring as maximal keratometry (Kmax). In this study the flattest, steepest and maximal radius of the cornea are taken from the anterior curvature sagittal map of the cornea. The corneal thickness values, central and thinnest, are taken also from this map. With the advancement of keratoconus steepest, flattest and K max increase. Central and thinnest values of pachymetry are decreasing.
After cross-linking procedure we noted the following changes:

  • the flattest keratometry significantly reduces 6 months after cross-linking and continues to reduce even after 3 years (flattening 3.8 D).
  • steepest keratometry significantly reduces 6 months after cross-linking and continues to reduce even after 3 years (flattening 3.36 D)
  • maximal keratometry significantly reduces 6 months after cross-linking and continues to reduce even after 3 years (flattening 6 D) .
  • there is a tendency of stabilizing UCVA after crosslinking and even an increasing 1/10, 3 years after procedure
  • there is a tendency of continuous increasing of BCVA especially starting 6 months after procedure and continuing even after 3 years with 2/10
  • Central pachymetry values continue to low until 3 years after cross-linking. This phenomenon is known as “Corneal shrinking”. Cornea stiffens and became stronger, opposing to the deforming tendency of the keratoconus

In other studies, visual acuity generally starts to improve 3 months after cross-linking (10) following a temporary reduction in early phase due probably to corneal haze and edema. Visual acuity improvement has been reported from 1 to 2 Snellen line 1- 4 years after treatment (11,12).
The reduction in keratometric values by 2 diopters and gradually improving in UCVA and BCVA has been reported in long term studies (11). Other randomized clinical studies have shown evidence of arrested keratoconus with improvements in keratometry values and visual acuity (13).
In our study the most important findings were the reduction of 3 diopters and more in flattest and steepest keratometry and a reduction of 6 diopters in maximal keratometry. Also an increase in 1/10 in UCVA and 2/10 in BCVA is noted.


Cross-linking procedure shows to be effective in reducing corneal radius (flattest, steepest, maximal). Having a flatter cornea in a progressive keratoconus means that the progress of keratoconus is stopped and there is also a remodeling of its surface. Remodeling of the cornea, also stabilizes visual acuity and even improves best spectacles corrected visual acuity.

Aims: To analyze the data and to assess the efficacy of cross-linking in stopping keratoconus progression.

Patients and methods: 81 eyes with progressive keratoconus were treated with epithelium off cross-linking method. Patients were followed for a period of 3 years after treatment, recording the following parameters: flattest, steepest and maximal keratometry; central and thinnest pachymetry, uncorrected visual acuity (UCVA), and best corrected visual acuity (BCVA).

Results: Clear reduction in keratometry values, increasing in BCVA, UCVA starting 6 months after procedure and continuing also 3 years after it.

Conclusion: Cross-linking seems to be effective in flattening the keratoconic cornea and stabilizing the corneal structure and therefore improving visual acuity

  1. Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998;42:297–319
  2. Auffarth GU, Wang L, Völcker HE. Keratoconus evaluation using the Orbscan topography system. J Cataract Refract Surg 2000;26:222–8.3- Prisant O, Legeais, Renard G. Superior keratoconus. Cornea 1997;16:693–4.
  3. Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984; 28:293–322.
  4. Newkirk K. M., Chandler H. L., Parent A. E., et al. Ultraviolet radiation-induced corneal degeneration in 129 mice. Toxicologic Pathology. 2007;35(6):819–826
  5. Podskochy A., Gan L., Fagerholm P. Apoptosis in UVexposed rabbit corneas. Cornea. 2000;19(1):99–103.
  6. Millodot M., Shneor E., Albou S., Atlani E., GordonShaag A. Prevalence and associated factors of keratoconus in jerusalem: a cross-sectional study. Ophthalmic Epidemiology. 2011
  7. Gordon-Shaag A, Millodot M,Shneor E,Liu Y. Biomed Res Int. 2015; 2015: 795738 The Genetic and Environmental Factors for Keratoconus
  8. Rahmen W, Anwar S. An unusual case of keratoconus. J Pediatr Ophthalmol Strabismus 2006;43:373–5.
  9. Spoerl E, Huble M, Kasper M, Sieler T. Increased rigidity of cornea caused by intrastromal cross-linking. Ophthalmologe. 1997;94:902–6
  10. Mazotta C, Balestrazi A, Baiocchi S, Traversi C, Caporossi A. Stromal haze after combined riboflavin-UVA corneal collagen cross-linking in keratoconus: In vivo confocal microscopic evaluation. Clin Experiment Ophthalmol. 2007;35:580–2.
  11. Caporossi A, Mazzotta C, Baiocchi S, Caporossi T. Long-term results of riboflavin ultraviolet A corneal collagen cross-linking for keratoconus in Italy: The Seina eye cross study. Am J Ophthalmol. 2010;149:585–93. [PubMed]
  12. Raiskupf-Wolf R, Hoyer A, Spoerl E, Pillunat L. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: Long term results. J Cataract Refract Surg. 2008;34:796–801.
  13. Wittig-Silva C, Whiting M, Lamoureux E, Lindsay LG, Sullivan LJ, Snibson GR. A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: Preliminary results. J Refract Surg. 2008;24:S720–5

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