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Does another family member have Keratoconus ?
At what age were you diagnosed with Keratoconus ?
Personalized, Customized, Individualized Keratoconus Care because "One Size Doesn't Fit All"
CXL - Corneal Crosslinking
News from Leading American Ophthalmologist - Arun C. Gulani, M.D.

In  anticipation of CXL approval in the USA, ophthalmologists are looking forward to addressing Keratoconus with renewed vigor.

Dr. Gulani is a world renowned eye surgeon and Lasik specialist. Former Chief of the Cornea service and Asst. Professor at University of Florida, School of Medicine; he is Founding Director of the Gulani Vision Institute.

Given Dr. Gulani’s approach to Keratoconus involving over 12 surgical approaches and combinations therein, the wide spectrums of applications are only limited by our logic and imagination e.g. Laser followed by CXL, INTACS followed by Laser and CXL, ICL followed by Laser followed by CXL, Cataract surgery with Toric Lens Implant followed by Laser followed by CXL. I also want to point out that by logic, I do mean responsible thinking and knowledge of anatomy, optics and physiology in selecting the most appropriate surgery or surgeries and keeping in mind that they be synergistic towards a visual goal.

Approaching the cornea of a patient with Keratoconus as an asymmetric high irregular astigmatism and by applying specific inclusion criteria, we are not only clear in our head about the treatment as  refractive surgeons but we are helping patients to understand that keratoconus is an approachable condition despite its progressive nature, and that there are surgical options at every stage to help the patient live a continued, productive life.

Applying our classification system we can therefore address practically all presentations of Keratoconus directly for best vision while in some cases, we may need to build the cornea in strength, perform scar removal and tissue replacement such as Lamellar Keratoplasty or Penetrating Keratoplasty and then present for Excimer laser surgery  (Classification system Class I) or in specific cases we can prepare in a cataractous age population to customize their cataract surgery in manipulating the optics intra ocularly (ie. Toric IOL) and then addressing the final refractive residual error on the cornea.

CXL a mandated stage II following the reshaping of Keratoconus?

Dr. Gulani envisions a future wherein a Keratoconic cornea once brought to its desired shape by the Excimer Laser in a PRK / ASA mode, INTACS (Gulani AC. INTACS : A Refractive Surgery to Prepare and Repair. INTACS Round Table. American Society of Cataract & Refractive Surgery Conference, May 2007) or Conductive keratoplasty  or even after corneal building procedures like Lamellar Keratoplasty followed by Excimer PRK/ASA, can then undergo CXL treatment for cross linking into a more stable and long lasting effect.

The use and indications for CXL will only expand as we use it not only for primary treatments but also for solidifying modified shapes as a secondary mandated procedure. For example, applying CXL, can also be done on a Keratoconic cornea treated previously with conductive keratoplasty (Class II e.).

Studies are needed for long term impact to make Stage II CXL a future mainstream application.

These very principles follow the concepts that have been brought together under Dr. Gulani’s concepts of Corneoplastique™ wherein topical, brief, elegant, aesthetically pleasing, least invasive surgeries are used singly or in stages towards a goal of unaided emmetropia. Corneoplastique™ prepares for the final fine tuning using the Excimer Laser towards a visual goal where early rehabilitation and aesthetic outcomes are essential, with promising uncorrected visual acuity.

Safety and individual case selection criteria are mandatory, in such customized approaches to Keratoconic cases.

Dr. Gulani recently published a book chapter on CXL (Ref 2 &3) and has shared his concepts and innovative thoughts for fellow eye surgeons worldwide as the arrival of CXL opens new avenues and consolidates previously configured approaches to effectively address this relentless disease.

New Keratoconus related Publications of Dr.Gulani:

1. Gulani AC, Gulani AC, Holladay J, Belin M, Ahmed I. Future Technologies - Pentacam Advanced Diagnostic. In Experts Review of Ophthalmology - London (in Press).

2. Gulani AC, Nordan L. Advances in Corneoplastqiue: Art of Laser Vision Surgery.

Mastering Corneal Collagen Cross Linking Techniques. Textbook of Ophthalmology. JP Inc. 2009; 56-63, 11.

3. Gulani AC, Boxer Wachler B. ReShaping Keratoconus: laser PRK followed by Corneal Cross Linking. Mastering Corneal Collagen Cross Linking Techniques. Textbook of Ophthalmology. JP Inc. 2009; 120-131, 19.

4. Gulani AC. Irregular Astigmatism: Management in Unstable Cornea

Textbook of Irregular Astigmatism. Slack Inc. 2007; Slack Inc

5. Gulani AC. Laser Vision Surgery for Keratoconus
Textbook of Keratoconus. Slack Inc. 2009; Slack Inc (in Press)

Produced Exclusively for KC Global: Courtesy of Gulani Vision Institute

San Francisco 2009: American Academy of Ophthalmology
Vision-Related Quality of Life in Keratoconus Patients Treated for Corneal Collagen Crosslinking

Location: San Francisco 2009 AAO, Moscone Center, Room: South 238.

Presenting Author: Ricardo Gomes dos Reis MD.

Co-Authors: Adalmir M Dantas MD, Haroldo V Moraes Jr MD, Ricardo Lamy MD, Mariana G Pecego MD, Camila F Netto MD, Bruno P Procopio Da Silva, MD, Lorena Vianna.

Purpose: Evaluate the vision-related quality of life in keratoconus patients treated with riboflavin and ultraviolet radiation for Corneal Collagen Cross-linking (CXL).

Methods: The National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) was applied in twenty-one patients with progressive keratoconus treated by CXL. The questionnaire was applied before and after the procedure, with ranges of 3, 6 and 12 months.

Results: The NEI-VFQ-25 composite score increased 5,3 points after 3 months (P<0,05); 4,2 points after 6 months (P<0,05) and 5,4 points after 12 months (P<0,05).

Conclusion: The vision-related quality of life had a general improvement after cross-linking treatment.

Effects of Corneal Collagen Crosslinking on Visual Acuity and Contrast Sensitivity

 Location: San Francisco 2009 AAO, Moscone Center, Room: South 238

Presenting Author: Ricardo Lamy MD.

Co-Authors: Adalmir M Dantas MD, Haroldo V Moraes Jr MD, Mariana G Pecego MD, Camila F Netto MD, Ricardo Gomes dos Reis MD, Bruno P Procopio Da Silva, MD, Lorena Vianna.

Purpose: Assess the effects of corneal collagen crosslinking (CXL) on visual acuity and contrast sensitivity.

Methods: Sixty two eyes of 31 patients were enrolled. One eye was treated and the fellow served as control. Pelli-Robson contrast sensitivity test (PR) and best corrected visual acuity (BCVA) were compared preoperatively and 40, 90, 180 and 365 days after cross-linking.

Results: In the treated group, BCVA (logMAR) improved (P<0,05) after 40 days (-0,08); 90 days (-0,14); 180 days (-016); 365 days (-0,18) and PR decreased -0,13 points (P=0,34) after 40 days and increased +1,23, +1,81 and +2,35 points after respectively 90, 180 and 365 days (P<0,05).

Conclusion: CXL was efficacious in improving visual acuity and contrast sensitivity.

American Academy of Ophthalmology 2009

The Influence of High-dose Cortisol on the Biomechanics of the Cornea
Eberhard Spoerl, PhD; Viktoria Zubaty, MSc; Naim Terai, MD; Lutz E. Pillunat, MD;
Frederik Raiskup, MD, PhD

Purpose: To investigate the change in biomechanical properties of the cornea induced by high-dose hydrocortisone.

Methods: The influence of hydrocortisone was investigated in 12 fresh porcine corneas incubated in culture medium of 2.5 μM of hydrocortisone for 7 days. Twelve additional porcine corneas incubated in culture medium without hydrocortisone for the same time served as the control group. Strips of cornea were cut and the stress–strain relationship was measured in a biomaterial tester. Young’s modulus was calculated.

Results: After incubation, the thickness of the cornea was 11206130 μm in the control group and 1320690 μm in the hydrocortisone group. The hydrocortisonetreated corneas were 18% thicker compared to the control corneas. However, the difference in the biomechanical stress value at 10% strain was significantly larger. In the control group, the stress value measured 122640
kPa, and in the hydrocortisone group, it measured 77619 kPa (P=.003), representing a reduction of the corneal stiffness by 37% due to hydrocortisone treatment. Young’s modulus was reduced by 42.8% from 2.9061.10 MPa in the control group to 1.6660.49 in the hydrocortisone group.

Conclusions: Hydrocortisone is a modulating factor of the biomechanical properties of the cornea. The significance of the cortisol status of the patient and its influence on the biomechanical stability of the cornea should be considered in the development of keratectasia in keratoconus or after refractive surgery.

 [J Refract Surg. 2009;xx:xxx-xxx.] doi:10.3928/1081597X-2009 

In the Line of Sight: News in the Pentacam Software



During the ASCRS in Chicago Oculus has presented two unique software features of the Pentacam:

  • Belin/Ambrosio Enhanced Ectasia Screening, developed by Prof. Michael Belin, MD, Albany/New York and Renato Ambrosio, MD, Rio de Janeiro/Brazil,
  • 3D lens densitometry with the Pentacam Nucleus Staging called “PNS”, developed by Donald Nixon, MD, Ontario/Canada.

“The goal of the Belin/Ambrosio Enhanced Ectasia Display is, to combine elevation based mapping and pachymetry corneal evaluation in an all inclusive display”, says Prof. Michael Belin one of the clinical investigators.

A new method is used to fit the sphere to the cornea called the enhanced BFS. It offers two main advantages:

  • A cone in an early stage of Ectasia or Keratoconus is more pronounced
  • A elevation map of normal eyes (eg. an astigmatism) looks same with the common BFS and the enhanced BFS. Only irregularities like early Ectasia are more pronounced. 

The pachymetry progression analysis is already included in the Pentacam software and well known. Together with the enhanced BFS it completes this display. “We found that Keratoconus patients have thinner corneas and faster and more abrupt increase of corneal thickness progression than normal corneas. These findings were in agreement with previous reports in the literature pioneered by Mandell and Polse. Interestingly, these new parameters are effective in detecting abnormalities in the majority of eyes with normal anterior curvature maps in patients with keratoconus in the contra-lateral eye. Thus, these parameters increase our sensitivity to detect Ectasia and its susceptibility. However, the enhanced display has increased our specificity to detect not ecstatic cases with inferior steepening” says Dr. Renato Ambrosio the second clinical investigator.

More than 800 eyes were examined in Rio de Janeiro/Brazil, Ankara/Turkey and Albany/USA to define the borderline numbers.

The investigation and interpretation of the display is intuitive:

  • If the corneal thickness progression shows an average index higher 1.1 the increase of thickness progression is clinically significant and the red curve is not parallel to the black broken lines but steeper and...
  • If the difference map between the BFS and the enhanced BFS elevation map shows a red center it is clinically significant as well.

The evaluation of the crystalline lens conditions in terms of opacifications is clinical routine. There are lens opacification systems like the LOCS grading but it still subjective and open to interpretation. Another question is: what are the most efficient Phaco settings.

The Pentacam measures the lens density in an objective, reproducible and accurate. “The new software measures a 3D template volume and optical density to generate a nuclear cataract grade”, says Dr. Donald Nixon the clinical investigator of this project. More than 300 patients were included into the clinical studies in Ontario/Canada which were done with the AMO Signature Phaco System linked to the Pentacam Nucleus grading system. The results are very promising, because:

  • Significant less EPT and BSS was used with Pentacam guided settings
  • The needle time significantly less in grade 4-5 cataracts.

These results were confirmed and presented during the ASCRS in Chicago by T.M.Rabsilber, MD member of the refractive group leaded by Prof. G.U. Auffarth, MD at the University of Heidelberg, and Prof. Ekkehard Fabian, MD, AugenCentrum Rosenheim.


 PENTACAM® Basic  1.59 MB PDF

Produced Exclusively for KC Global: Courtesy of OCULUS Optikgeräte GmbH


The SynergEyes® KC Hybrid Contact Lens for Keratoconus


SynergEyes® KC is the first FDA-cleared hybrid contact lens specifically designed for patients with keratoconus.


SynergEyes® KC utilizes revolutionary hybrid technology, combining a rigid center with a soft outer skirt. The "breathable" rigid center of the SynergEyes® KC lens promotes corneal health while providing the vision you need to improve your quality of life. The soft skirt keeps the lens in place, reducing or eliminating mechanical rubbing and enhances your level of comfort, making this a perfect contact lens solution for patients with keratoconus.


Unlike traditional soft or rigid lenses, the SynergEyes® KC lens delivers consistent vision and contact lens stability. No other contact lens on the market currently provides these benefits, in a single product. The SynergEyes® KC and the ClearKone lens (The ClearKone version was designed specifically to vault above the eye's cone shape for increased comfort) makes having to choose between comfort and visual clarity a thing of the past.

Produced Exclusively for KC Global: Courtesy of SynergEyes®, Inc

The New Frontiers of Ophthalmology: “REGENERATIVE MEDICINE”
A Treatment Able To Regenerate Ocular Tissues Using
Autologous STEM CELLS

By: Massimo Lombardi
Patrizia Belilli
663.75 KB

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Keratoconus Member is Better, Stronger, Faster, at the California International Marathon

"As for the race itself, what a difference training makes. This time around I ran nearly 900 training miles (vs. 500 leading up to the San Diego marathon), logged three 20-milers (vs. one 20-miler last time), and read, read, and read some more about running. So I actually knew what I was doing and was well prepared for it."

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 Ultraviolet A/Riboflavin Corneal Cross-linking for Infectious Keratitis Associated with Corneal Melts

Hans Peter Iseli, MD, Michael A. Thiel, MD, PhD, Farhad Hafezi, MD, PhD, Juergen Kampmeier, MD, and Theo Seiler, MD, PhD. 

Purpose: To evaluate the efficacy of ultraviolet-corneal crosslinking (CXL) for treating infectious melting keratitis.

Methods: Five patients with infectious keratitis associated with corneal melting were treated with CXL at the outpatient departments of the Institut fur Refraktive und Ophthalmo–Chirurgie and the eye hospital at the University of Zurich. CXL was performed when the infection did not respond to systemic and topical antibiotic therapy. Follow-up after cross-linking ranged from 1 to 9 months.

Results: In all cases, the progression of corneal melting was halted after CXL treatment. Emergency keratoplasty was not necessary in any of the 5 cases presented.

Conclusions: CXL is a promising option for treating patients with therapy refractory infectious keratitis to avoid emergency keratoplasty.

Anpassung formstabiler Kontaktlinsen nach Kollagenvernetzung bei Keratokonus

Carsten Avermann, Markus Kohlhaas

Der Keratokonus führt als erworbene zumeist progressive bilaterale zentrale oder parazentrale Keratektasie durch seinen hohen irregulären Astigmatismus oder durch stromale Hornhautnarben zu einer deutlichen Visusreduktion. In mehr als 20% der Patienten ist eine Visusrehabilitation in einem fortgeschrittenen Stadium nur noch durch eine perforierende bzw. eine tiefe lamelläre Keratoplastik möglich.

Die Quervernetzung der stromalen Kollagenfibrillen mittels Riboflavin und UV-A Bestrahlung (Hornhautvernetzung) scheint hierbei eine neue Therapieoption zur Vermeidung einer weiteren Progression mit konsekutivem signifikanten Visusverlust darzustellen.

Die Quervernetzung der Kollagenfibrillen durch Riboflavin und UVA Bestrahlung modifiziert die biomechanischen Eigenschaften der Hornhaut und führt hierdurch zu einer Verfestigung insbesondere der oberen 200-250 µm. Tiefer gelegene Strukturen werden nicht geschädigt. Die einfache Durchführung wie die geringen Behandlungskosten avisieren die Methode zu einer viel versprechenden Therapieoption insbesondere in Fällen einer zwar nachgewiesenen Progression jedoch bei noch akzeptabler Visussituation. Die Zahl der zur Visusrehabilitation notwendigen Keratoplastiken könnte hierdurch deutlich reduziert werden.

Keratoconus Treatment Parameters

Diagram Courtesy of the Inventors:  The University Eye Clinic, Dresden, Germany

International Keratoconus Highlights in 2008

By Our International News Correspondent

 Jenny Deva MD

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Equal To The Task: The International Congress of Corneal Cross Linking

December 5- 6th, 2008

 The 4th International CXL Congress - The Westin Bellevue Hotel, Dresden, Germany

CXL Congress 2008

A panorama view of some of the delegates at the 2008 CXL Congress

The strength of the International Congress of Corneal Cross Linking comes primarily from the strength of its people - the organizers and delegates - which made the Congress a outstanding success.

We could see this immensely, and it is also why, long before investing in anything else, from the beginning Keratoconus members started investing in it's people, the finest in the world. Experts with a truly international profile, many of them fluent in many languages. Experts highly prepared to understand the mysteries behind our eye condition, to ultimately eliminate Keratoconus as a health issue internationally.

We give our thanks to the congress organizers, and the delegates that came from all over the world who made this congress a unforgettable historical event. With it also being held for the first time in Dresden, Germany, the place where Corneal Crosslinking (the first ever treatment for Keratoconus) was invented, this made for a congress which was very uniquely memorable.

It was clear for all, the delegates at the congress are "Equal To The Task" to eliminate Keratoconus as a health Issue. More than 269 delegates of high standards in all from 41 countries. World-class Scientists, Internationally renowned Professors, World famous Ophthalmologists, Vision Investigators, Visual Researchers, it was the United Nations for the Cornea !

Thanks to their will and talent, the International Congress of Corneal Cross Linking has managed to put together a wide array of scientific exchange for delegates worldwide. A true boundless solution to discuss and communicate about Keratoconus treatments and technologies in a scientific information sharing atmosphere, which turn the International Congress of Corneal Cross Linking into a worldwide leader in the vision community.

They are a great team, no doubt. But what makes them really big it is simply one thing, their huge ambition to give patients the best possible out-comes. With the highest strictness, discipline, and creativity with Science and Technology.

Thanks to you all.

Safety, Quality & Teamwork  Safety, Quality & Teamwork

Corneal Collagen Crosslinking with Riboflavin and Ultraviolet A to Treat Induced Keratectasia after Laser  in Situ Keratomileusis

Farhad Hafezi, MD, John Kanellopoulos, MD, Rainer Wiltfang, MD, Theo Seiler, MD, PhD

Purpose: To determine whether riboflavin and ultraviolet-A (UVA) corneal crosslinking can be used as an alternative therapy to prevent the progression of keratectasia.

Setting: Institute for Refractive and Ophthalmic Surgery, Zurich, Switzerland, and a private clinic, Athens, Greece.

Methods: Corneal crosslinking was performed in 10 patients with formerly undiagnosed forme fruste keratoconus or pellucid marginal corneal degeneration who had laser in situ keratomileusis (LASIK) for myopic astigmatism and subsequently developed iatrogenic keratectasia. Surgery was
performed in 1 eye per patient.

Results: Crosslinking induced by riboflavin and UVA arrested and/or partially reversed keratectasia over a postoperative follow-up of up to 25 months as demonstrated by preoperative and postoperative corneal topography and a reduction in maximum keratometric readings.

Conclusion: Riboflavin–UVA corneal crosslinking increased the biomechanical stability of the cornea and may thus be a therapeutic means to arrest and partially reverse the progression of LASIK-induced iatrogenic keratectasia.

Collagen Crosslinking with Riboflavin and UVA-light in Keratoconus

Kohlhaas M.

Klinik für Augenheilkunde, St. Johannes-Hospital Dortmund, Johannesstrasse 9-17, 44137, Dortmund, Deutschland.

Reduced corneal mechanical stability in keratoconus and similar corneal diseases can be treated by photooxidative crosslinking of the corneal collagen. This method is currently undergoing clinical evaluation worldwide. To achieve high absorption of the irradiation energy in the cornea, riboflavin at a concentration of 0.1% and UVA light at a wavelength of 370 nm corresponding to the relative maximum of absorption of riboflavin (vitamin B2) is used. These therapeutic parameters were experimentally tested and have been proven clinically. Current data demonstrate that the therapeutic crosslinking procedure is safe when the important theoretical and clinical parameters are observed, and that progression of keratoconus can be prevented. In all, 80% of the published cases show a decrease in corneal curvature of about 2 D, which leads not only to stabilisation but also to an increase in visual acuity.

Ophthalmologe. 2008 Aug;105(8):785-96

Collagen Crosslinking with Riboflavin and Ultraviolet-A Light in Keratoconus: Long Term Results
Frederik Raiskup-Wolf, MD, Anne Hoyer, MD, Eberhard Spoerl, PhD, Lutz E. Pillunat, MD
Purpose: To prove the long-term dampening effect of riboflavin- and ultraviolet-A-induced collagen crosslinking on progressive keratoconus.

Setting: Department of Ophthalmology, C.G. Carus University Hospital, Dresden, Germany.

Methods: Four hundred eighty eyes of 272 patients with progressive keratoconus were included in this long-term retrospective study. The maximum follow-up was 6 years. At the first and all followup examinations, refraction, best corrected visual acuity (BCVA), corneal topography, corneal thickness, and intraocular pressure were recorded.

Results: The analysis included 241 eyes with a minimum follow-up of 6 months. The steepening decreased significantly by 2.68 diopters (D) in the first year, 2.21 D in the second year, and 4.84 D in the third year. The BCVA improved significantly (R1 line) in 53% of 142 eyes in the first year, 57% of 66 eyes in the second year, and 58% of 33 eyes in the first year or remained stable (no lines lost) in 20%, 24%, and 29%, respectively. Two patients had continuous progression of keratoconus and had repeat crosslinking procedures.

Conclusions: Despite the low number of patients with a follow-up longer than 3 years, results indicate long-term stabilization and improvement after collagen crosslinking. Thus, collagen crosslinking is an effective therapeutical option for progressive keratoconus. 

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 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 Corneal 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 technique 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 illumination 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 fruste keratoconus in the near future.

Prof Mannis continued his address 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

Leading American Sports Vision Doctor explains a "Lost" Art in RGP Contact Lens Fitting Techniques
Dr. Jeffrey J Eger OD, explains to us about a little known RGP Contact Lens fitting technique and the reported success achieved in using this fitting methodology, which he and his patients believes in passionately

Contact Lens Fitting of Keratoconus by Dr Eger

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New Horizons with up-to-date Medical Care and Treatment Options in Malaysia for Patients
Jenny P Deva MD explains to us about the Malaysian experience of Keratoconus and it's modern treatment, with a world-wide call for an "Alert On Keratoconus"

The Malaysin 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.

Estrogen-induced changes in biomechanics in the cornea as a possible reason for Keratectasia

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 {beta}-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 and 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.

The Dundee University Scottish Keratoconus study: demographics, corneal signs, associated diseases, and eye rubbing. 

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.

The Effect of Collagen Crosslinking Using Riboflavin/UVA on the Molecular and Fibrillar Architecture of the Corneal Stroma

Wednesday, Apr 30, 2008, 8:30 AM -10:15 AM:
Reviewing Code: 152 cornea: stroma and keratocytes - CO

Author Block:
K.M. Meek1, S. Hayes1, C.S. Kamma-Lorger1, C. Boote1, A.J. Quantock1, D. O'Brart2, J. Marshall2. 1Optometry & Vision Sciences, Cardiff University, Cardiff, United Kingdom; 2Department of Ophthalmology, St Thomas' Hospital, Kings College London, London, United Kingdom.

Keywords: 484 cornea: stroma and keratocytes, 480 cornea: basic science, 573 keratoconus

Purpose: To measure the changes in collagen interfibrillar spacing and intermolecular spacing in porcine corneas immediately following crosslinking with riboflavin/UVA.

Methods: 42 enucleated porcine eyes were treated using riboflavin/UVA crosslinking following the methods described by Wollensak et al. (Am J Ophthalmol. 2003;135:620-7). After crosslinking, the corneas with a small scleral rim attached, were dissected and examined at the Daresbury synchrotron radiation source. Both small angle and wide angle x-ray scattering studies were performed to measure the central average interfibrillar spacing and the average intermolecular spacing respectively.

Results: There was a reduction in the interfibrillar spacing from 65.9±1.4nm to 60.1±1.8nm after riboflavin/UVA treatment. The intermolecular spacing, however, increased from 1.63± 0.00nm to 1.78 ±0.08nm.

Conclusions: Comparison of the results with those from groups where either riboflavin or UVA treatment was omitted, allowed us to conclude that the reduction in the interfibrillar spacing is due to riboflavin treatment, probably a dehydration effect of the dextran used in the vehicle. The increase in the intermolecular spacing was due to crosslinking, as it only occurred when both riboflavin and UVA were used. Previous studies have revealed that crosslinking collagen fibrils (by natural ageing or by glycation) increases the spacing between the molecules. The present results confirm that the majority of the collagen molecules in the stroma are crosslinked by this treatment.

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