Evolution of Surgery for Keratoconus - The Singapore Eye Foundation Lecture

Professor Mark Mannis, University of California

 
Presented at the Inaugural Asia Cornea Society Meeting, Singapore on 14-3-08
 

A summary by our International Scientific News Correspondent

 Jenny Deva MD

Professor Mannis started his talk by saying that the management of Keratoconus has always been both Optical and Surgical. Optical devices including controlled physical pressure on the eyes and even Contact Lenses made of glass from as early as 1880’s was used in the treatment of Keratoconus. The Surgical Procedures includes Corneal Flattening devices such as, Intracorneal Rings, Implantable Contact lenses, Penetrating Keratoplasty, Deep ALK, Laser enabled Keratoplasty and of course Collagen Cross Linking (CXL) being the most recent.

In the historical perspective Prof Mannis mentioned how even leeches were used medicinally and applied around the forehead. Then surgeons like Von Grafe applied Silver Nitrate, while others like Elschnig applied heat and cautery to the apex of the cone, then to the periphery all aiming at flattening the cornea. Castroveijo designed a square corneal graft in the late 1950’s. Prof. Sato of Japan attempted correction by doing Internal Keratotomy, but this proved disastrous as the corneas ended in Bullous Keratopathy.

Later Epikeratoplasty was done for Keratoconus. This was evolved to Deep Anterior Lamellar Keratoplasty (DALK). Intraconeal Corneal Rings have been used with satisfactory results, but in a narrow range of appropriate patients. It however has some Refractive Stability.

Now the latest surgical technology is Collagen Cross Linking (CXL) . This can be done in early Keratoconus, as the Ultraviolet Light Radiation produces Covalent Bonding of the Collagen Fibrils, thus increasing the biomechanical strength of the thinning weakened cornea. Personally I believe this may really become suitable as a proactive and preventive treatment for early detected Keratoconus or Forme Keratoconus in the near future.

Prof Mannis continued to say that though surgical procedures help solve the problems at hand, they however do not address why in the first instance a tissue defect in Keratoconus arises. This is of course leads us to question the congenital and hereditary gene factor which can result in the biomechanical weakening of the cornea. He ended on a note that the future of Keratoconus lies perhaps in “Genome Mapping” and “Gene Therapy”.

This presentation was well illustrated and it was an eye opener to the fact that no real “fool-proof” technique or procedure has become, as yet, the treatment of choice for Keratoconus. Further research is still needed to help us find a long lasting solution for that same length of time, from which to go beyond the existing and current mainstream treatment options for Keratoconus. In other words the search for a complete cure is on.

Reported by Jenny Deva MD

Contact Lens Fitting of Keratoconus by Dr Eger

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The Malaysian Experience

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Enzymatic evidence of the depth dependence of stiffening on riboflavin/UVA treated corneas
 

Schilde T, Kohlhaas M, Spoerl E, Pillunat LE

Universitäts-Augenklinik Carl Gustav Carus, Fetscherstraße 74, 01307, Dresden, Germany.

Purpose: It has been shown that the treatment of keratoconus with riboflavin/ultraviolet A (UVA) causes significant stiffening of the cornea due to cross-linking. The aim of this study was to evaluate how deep the mechanical stabilization after collagen cross-linking could be shown biochemically.

Method: Ten out of 20 enucleated porcine eyes were treated with riboflavin as a photosensitizer and UVA (370 nm, 3 mW/cm(2), 30 min). The other 10 eyes served as controls. With a Microkeratom device, two flaps with a thickness of 200 microm and a diameter of 8 mm were cut off from each eye and put in a collagenase solution (NaCl plus collagenase A, 1:1). The surfaces of the flaps were measured digitally every day to characterize the dissolving behavior.

Results: The resistance (regarding corneal collagen against enzymatic digestion) of the treated superficial flaps was considerably higher (p=0.001) compared to those that were cut secondarily and to the control flaps. But even the flaps from deeper layers showed a significant increase in resistance (p=0.02) compared with the untreated flaps. The half-life of the surfaces of the treated superficial flaps was 220 h; of those cut secondarily, it was 80 h. Both untreated flaps had a half-life of 50 h.

Conclusions: The biochemical study showed that the treatment of the cornea with riboflavin/UVA leads to significant collagen cross-linking not only in the anterior slice of 200 microm but also in the following 200 microm. This locally limited cross-linking effect may be explained by the absorption behavior for UVA of the riboflavin-treated cornea; 65% of UVA irradiation is absorbed in the first 200 microm and only 25-30% in the next 200 microm. Therefore, deeper-lying structures and especially the endothelium are not affected.

Eberhard Spoerl, Viktoria Zubaty, Frederik Raiskup-Wolf and Lutz E Pillunat

Department of Ophthalmology, University Dresden, Germany.

Accepted 14 June 2007

Aim: The risk of regression after PRK and the tendency to develop keratectasia after LASIK procedure is higher in women. Currently interest is focused on the influence of estrogen on corneal stability after corneal refractive surgery. The aim of this experimental study was to investigate the change in biomechanical properties of the cornea induced by estrogen

Methods: The influence of estrogen was investigated in 12 fresh porcine corneas incubated in culture medium with 10µM of -estradiol for 7 days. A group of 12 porcine corneas incubated in culture medium without estradiol for the same time served as a control group. Strips of cornea were cut and the stress-strain was measured in a biomaterial tester. The Young's modulus was calculated. 

Results: During incubation the thickness of the cornea changed in the control group by only 6.4% and in the estradiol group by 12%. However, the difference in the biomechanical stress values at 10% strain was significantly larger. In the control group was the stress value measured 120.18 ± 28.93 kPa and in the estradiol group 76.87 ± 34.63 kPa (p=0.002), representing a reduction of the corneal stiffness by 36% due to the estradiol treatment.

Conclusion: Estrogen is a modulating factor of the biomechanical properties of the cornea which is not explainable only by an increased swelling. The significance of the hormone status of patients and its influence on the biomechanical stability of the cornea, a determining factor after refractive surgery, have been underestimated and may contribute to the development of keratectasia.

 
Keratoconus: age of onset & natural history
 

Dept of Optics University of Granada Spain.

• Olivares Jimenez JL,
• Guerrero Jurado JC,
• Bermudez Rodriguez FJ,
• Serrano Laborda D.

Keratoconus is a corneal dystrophy that degrades the optical function of the cornea. The onset of the process manifests optical signs: evolving astigmatism, failure of optical correction by spectacles, and distorted images. We report data from 74 keratoconus patients in need of keratoplasty. The variables studied included sex, age of onset, and refractive error. We find that the average age of the appearance of keratoconus is the second decade of life (mean age of onset = 15.39 years, SD = 3.95), with earlier onset occurring in females that in males, although the differences are not statistically significant. The mean corneal astigmatism before keratoplasty was 4.07 D (SD = 1.57). Optometrists should refer patients for surgery when all optical treatment has failed.

Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee, Scotland, UK

• Weed KH,
• Macewen CJ,
• Giles T,
• Low J,
• McGhee CN.

Aim

To investigate and correlate the corneal, refractive, topographic and familial characteristics of a large cohort with keratoconus.MethodsProspective observational study of 200 consecutive patients presenting with keratoconus during the 4 year-period 1997-2000. Subjects were examined at enrolment and at a final review. Data were collected on demographic characteristics, referral route, symptoms, refractive correction, eye rubbing, family history, medical history, slit-lamp biomicroscopic corneal signs, and computerized corneal topography.

Results

Mean age at enrolment was 30.9+/-10.4 (range, 12.2-72) years (N=200, 62.5% male, 93% white Caucasian) with a 5% family history of keratoconus. Atopic diseases included asthma (23%), eczema (14%), and hay fever (30%). Only 9% wore contact lenses before referral. Mean follow-up was 1004 days +/-282 (range, 390-1335) and 9.7+/-8.9 (range, 1.1-60) years from diagnosis. The mean simulated K1 corneal power at enrolment was 51.74+/-5.36 (range, 42.59-67.32) D and 88.5% exhibited bilateral keratoconus. Fifty-three (15%) topographically confirmed cones exhibited no clinical corneal signs at presentation. At enrollment, 56% had a pachymetry <0.480 mm increasing to 77% at final review. Forty-eight percent of subjects reported significant eye rubbing and there was a highly statistically significant difference (two sample t-test P=0.018) between keratoconus and control groups. TMS-2 axial corneal power was strongly associated with corneal scarring and age at diagnosis. The size of the scarring effect was 2.2 D (95% confidence interval (CI) 1.34, 3.06).

Conclusions

This study provides an overview of a large population with keratoconus highlighting presenting features and clinical and topographic progression over a 4 year-period.