Ординатура / Офтальмология / Английские материалы / Mastering Corneal Collagen Cross Linking Techniques (C3-R, CCL, CxL)_Garg_2009
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
5.Measure corneal thickness at thinnest point after 30 min of riboflavin application. If under 400 µm, use hypotonic riboflavin solution without dextran (310.7 mOsm/l) to enforce swelling of the cornea. Apply 2 drops every 30 seconds until corneal thickness is at least 400 µm.
6.As an additional safety feature, the output energy intensity can be checked prior to each treatment using the UV light meter that is delivered with the system (Figure 10.5).
7.The irradiating source is placed 5 cm from the cornea’s center and applied for 30 minutes (Figure 10.6). The 370 nm wavelength allows approximately 93% of UV light to be absorbed into the cornea, thus, there is no risk for damage to the lens and retina. The UVA light interacts with the riboflavin, producing reactive oxygen molecules that cause the formation of chemical bonds between and within the corneal collagen fibrils, making them stiffer.
8.During irradiation treatment, a drop of riboflavin solution is applied every 5 minutes to sustain the necessary concentration of riboflavin and prevent desiccation of the cornea (Figure 10.7).
9.The surgeon keeps the cornea moist with a drop of balanced salt solution every 2 minutes.
10.At the conclusion of the procedure, the patient receives topical antibiotic and a bandage contact lens is applied for 72 hours or until corneal reepithelization is complete. This is followed by application of fluorometholone 0.1% eyedrops twice daily for 6 weeks. If necessary, artificial tears are prescribed.
SAFETY
Corneal cross-linking is considered to be a safe procedure, provided the recommended safeguards are observed.
1.A clinically used UV source should ensure a perfect homogenous irradiance. Hot spots may cause local damages of endothelium cells especially in thin corneas.
2.The irradiated area of the cornea must be limited to 8 μm. Only the cornea is irradiated. Sclera, goblet cells and limbus are not treated.
3.The following treatment parameters are chosen to reach a strong cross-linking effect and to avoid
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damages of the adjacent tissues: |
Figure 10.5: Intensity check prior to each treatment
Figure 10.6: UV-A illumination of the cornea (Courtesy of Prof.Theo Seiler)
Figure 10.7: During UV-A irradiation, a drop of riboflavin solution is applied every 5 minutes (Courtesy of Prof.Theo Seiler)
CORNEAL COLLAGEN CROSS-LINKING WITH RIBOFLAVIN AND ULTRAVIOLET-A LIGHT: STEP BY STEP TECHNIQUE
•Wavelength: 370 nm
•Irradiance: 3mW/cm2 (Dose: 5.4 J/cm2)
•Irradiation time: 30 minutes.
4.To avoid high absorption of UVA in the cornea:
•Remove the diffusion barrier (epithelium).
•Minimum corneal thickness has to be 400 μm after removal of the epithelium.
•Concentration of riboflavin must be 0.1%.
•Diffusion time of riboflavin has to be 20-30 min.
MORE RESEARCH REQUIRED
We believe that collagen cross-linking might become a standard treatment for progressive keratoconus. Longterm studies must exclude serious late complications and confirm the durability of the stiffening effect.
Currently available published data, unpublished data, and personal observations by current international investigators make a convincing argument that collagen cross-linking is significantly safer than corneal transplantation.
In the current situation, there are not yet enough data available to establish a list of indications and contraindications. A potential clinical acceptance of the procedure requires the results of prospective controlled studies that are currently underway.
In the future, we may be able to further improve vision by combining the cross-linking procedure with procedures such as intracorneal ring implantation, orthokeratology, topography-guided photorefractive keratectomy, and conductive keratoplasty, an area that is under clinical research. Other possibilities which are under investigation include stabilizing cornea after radial keratotomy, and treating corneal edema and bullous keratopathy.
REFERENCES
1.Seiler T, Spoerl E, Huhle M, Kamouna A. Conservative therapy of keratoconus by enhancement of collagen crosslinks. Invest Ophthalmol Vis Sci 1996;37:S1017.
2.Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res 1998;66:97-103.
3.Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A- induced collagen cross-linking for the treatment of keratoconus. Am J Ophthalmol 2003;135:620-27.
4.Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after
riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg 2003;29:1780-5.
5.Spoerl E, Wollensak G, Seiler T. Increased resistance of cross-linked cornea against enzymatic digestion. Curr Eye Res 2004;29:35-40.
6.Wollensak G, Wilsch M, Spoerl E, Seiler T. Collagen fiber diameter in the rabbit cornea after collagen cross-linking by riboflavin/UVA. Cornea 2004;23(5):503-507.
7.Wollensak G, Spoerl E, Reber F, Seiler T. Keratocyte cytotoxicity of riboflavin/UVA-treatment in vitro. Eye 2004;18(7):718-22.
8.Pinelli, R. C3-Riboflavin for the treatment of keratoconus.
JCataract and Refractive Surgery Today Europe 2006;1:4950.
9.Caporossi A, Baiocchi S, Mazzotta C, Traversi C, Caporossi
T.Parasurgical therapy for keratoconus by riboflavinultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study.
JCataract Refract Surg 2006;32:837-45.
10.Wollensak G. Cross-linking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol 2006;17:356-60.
11.Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of crosslinks in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg 2006;32:279-83.
12.Mazzotta C, Traversi C, Baiocchi S, Sergio P, Caporossi T, Caporossi A. Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation. Eur J Ophthalmol 2006;16:530- 5.
13.Hafezi F, Kanellopoulos J, Wiltfang R, Seiler T. Corneal collagen cross-linking with riboflavin and ultraviolet A to treat induced keratectasia after laser in situ keratomileusis..
JCataract Refract Surg 2007;33(12):2035-40.
14.Hafezi F, Iseli HP. Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking. J Cataract Refract Surg 2008;34(7):1219-21.
15.Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen cross-linking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg 2008;34(5):796-891.
16.Kohnen T. Riboflavin-UVA corneal collagen cross-linking as an evolving surgical procedure for progressive ophthalmic tissue diseases. J Cataract Refract Surg 2008;34(4):527.
17.Mencucci R, Mazzotta C, Rossi F, Ponchietti C, Pini R, Baiocchi S, Caporossi A, Menchini U. Riboflavin and ultraviolet A collagen cross-linking: in vivo thermographic analysis of the corneal surface. J Cataract Refract Surg. 2007;33(6):1005-08.
18.Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. Collagen fibrils in the human corneal stroma:Structure and aging. Invest. Ophthalmol. Vis Sci 1998;39(3):644-48.
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ADVANCES IN CORNEOPLASTIQUETM: ART OF LASER VISION SURGERY
INTRODUCTION
The individual or combined use of amniotic membranes, glue, lamellar cornea, synthetics, i.e. INTACS, etc. and finally the Excimer laser as a sculpting tool towards an effort to perfect vision is what I wish to introduce as a new trend and possibly a superspecialty in eye care— Corneoplastique™.
Simply put, the ocular surface inclusive of the cornea (irrespective of the causative incident, i.e. LASIK complications/infection/trauma/previous surgery) is prepared by any one or a combination of the above techniques in single or multiple stages to prepare for the final fine tuning using the Excimer laser towards a visual goal where early rehabilitation and aesthetic outcomes are a welcome association with promising uncorrected visual acuity (Gulani AC, Corneoplastique™ Advanced Corneal Surgery Course. SASCRS-Durban, South Africa; Aug 2005).
This is in contrast to the more extensive standard surgical techniques like penetrating keratoplasties, etc. where in most cases the final unaided visual outcome despite a long rehabilitation period is less than optimal. Synergistically though, these standard surgeries, due to their proven track record can always serve as a backup plan in selection of any of the above mentioned techniques.
Corneoplastique™ includes all forms of laser vision surgery itself:
LASIK and various variants of laser vision surgery are performed on the cornea. It is important that refractive surgeons recognize the importance of the
ART of Laser Vision Surgeries by understanding the cornea and the whole spectrum of corneal surgery.
I remind LASIK surgeons that besides Technique and Technology, the third “T” is of equal, if not more importance and that is “Tissue” (in this case; Cornea).
Corneal surgical experience and knowledge will in all probability enhance the ability of a laser vision Surgeon to better select the candidacy of their patients, prevent complications and also prepare them to react in an efficient manner towards any inadequate/ unforeseen outcomes.
Similarly, these advanced corneal techniques can be used to even prepare patients who have had corneal problems like, corneal scars, pterygiums, previous surgeries like cataract surgery/corneal transplants/ radial keratotomy, etc. to make them suitable for laser vision surgery in a therapeutic mode towards a visual goal.
This ART of blending the full spectrum of ocular surface and corneal surgery in a therapeutic approach either before (To prepare the cornea) or after laser vision surgery (to repair the cornea) is the core function of this possible new superspecialty.
This ability to Prepare the cornea for laser vision surgery and to Repair the cornea from laser vision surgery using these techniques will raise the confidence of refractive surgeons and patients alike.
Indications for Corneoplastique™ would be the following:
1.Corneal scars (from previous surgeries / trauma / healed corneal ulcers / infections)
2.Pterygiums (advanced/ recurrent)
3.Previous surgeries (cataract surgery / corneal transplants / radial keratotomy, etc.)
4.Lasik and laser vision surgery complications
5.Corneal degenerations / dystrophies.
The art of blending the whole spectrum of surface ocular and corneal surgery using these topical, brief, aesthetic, and visually promising techniques either singly or in combinations shall raise the bar on making all surface surgeries visually focused.
CORNEOPLASTIQUE™ IN ACTION |
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What I want more surgeons to do is use less terminology |
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and more logic. “When I look at a complication it |
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does not matter to me what surgery was done or what |
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laser was used. I look at it as, here’s a cornea; what |
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does it have? Does it have a scar, irregular astigmatism, |
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is it thin, de-centered ablation, etc.? and approach that |
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problem accordingly”. |
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Using my recently introduced 5S system (Gulani |
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AC. 5S Classification System: ASCRS, California, March |
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2006) we can devise a plan to heal/repair the cornea |
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appropriately and finally fine tune using the Excimer |
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Laser (VISX Star S4 Santa Clara, CA). My goal all the |
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time is unaided 20/20. The 5Ss stand for shape, sight, |
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scar, site and strength. |
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This 5S system is an expansion of a three-level |
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corneal classification system I devised several years |
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ago (Flow chart 11.1).1 The three-level system was |
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based on the tissue components involved in the LASIK |
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surgery, and I assigned LASIK corneal complications |
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to Level I (corneal section), Level II (interface) or Level |
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III (ablation bed). This helped identify and treat a range |
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of corneal problems. |
MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
Flow chart 11.1: Gulani “5S” classification system
Similarly, the 5S system addresses questions about the cornea’s state in order to customize a treatment plan. It does not give importance to the technology used or the causative pathology itself.2
Here are its components:
1.Sight. Is the patient correctable to 20/20 with glasses and/or hard contact lenses?
2.Site. Is the involvement central or peripheral?
3.Scar. Is the cornea clear or scarred?
4.Strength. Is the cornea thin/ectatic (Keratoconus) or thick (Epikeratophakia/Bullous keratopathy)?
5.Shape. Is the cornea myopic (Steep), Hyperopic
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(Flat) or Astigmatic (Regular/Irregular)? |
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This 5S system allows you to understand, allocate |
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and plan a corrective approach in addition to your |
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knowledge of not only LASIK but lamellar corneal |
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surgery in general (LASIK is lamellar surgery, hence |
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any preparation or repair of the cornea for LASIK shall |
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usually involve a lamellar approach). Surgeons must |
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be familiar with the wide spectrum of advanced |
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surgical options available to provide the most |
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appropriate way to deal with a problem (Gulani AC, |
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Corneoplastique™: Art of Vision Surgery (Abstract). |
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ISOPT, Berlin, Germany, March 2006). The knowledge |
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of optics, anatomy, physiology and the combination |
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of these unchanged concepts can only be strengthened |
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with advancing technology. |
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For an example on how this concept works, let’s |
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take two cases and make a surgical plan: |
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1. Patient with LASIK ectasia: |
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Here the patient’s cornea basically has a problem |
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with three of the 5Ss, i.e. Strength, Shape and |
Sight. |
Stage I: Sutureless Lamellar Keratoplasty (Provides the Strength)—Remember to use a donor cap that is THICKER (Two reasons: remember the fact that the donor will deturgese and also that you will have more cornea to sculpt with the Excimer Laser at a later stage).
Stage II: Excimer Laser ASA (provides Shape and therewith Sight)
2.Now lets take a patient with an opposite problem. Aphakic Epikeratophakia with decentered, scarred epi-lenticle.
Here the cornea has a problem with all 5Ss (It is thicker (Strength), Scarred, central Site affected with poor Shape and Sight)
Stage I: Remove the epi-lenticle (Scar and Strength are addressed)
Stage II: Secondary IOL (Sight is addressed)
If needed further Stage III. Excimer laser to fine tune the Shape and further improve Sight.
Having personal experience with the full spectrum of vision corrective surgeries including presbyopic multifocal lenses like ReStor, Phakic Implants like the anterior, posterior and iris-supported IOLs, INTACS, etc. we can use these concepts universally to plan through the anterior chamber and cornea for final unaided vision.
New technology corneal surgical lasers, i.e. Intralase, Da Vinci, Femtec and Carl Zeiss are moving in this direction and I see them as an integral part of my Corneoplastique™ concept.
I could be planning a posterior lamellar transplant
– DLEK/DSAEK (My technique is called Key Hole Transplant) ReStor IOL, INTACS, Wavefront Lasik,
ADVANCES IN CORNEOPLASTIQUETM: ART OF LASER VISION SURGERY
Figure 11.1: Radial Keratotomy, Astigmatic Keratotomy, Hexagonal Keratotomy and previous Corneal Transplant. In all of these cases the S factor affected was Shape so the only treatment needed was excimer laser vision surgery for unaided emmetropia
Amniotic resurfacing, etc.; it does not matter as long as the sequence and stages of surgery make sense for a final outcome- Unaided emmetropia.
Also, at any stage we can always fall back on any of the traditional surgeries which will always be a backup for these patients, i.e. PKP, etc.
What we realize with the above examples and many more (Figures 11.1 to 11.7) is that we need to plan each stage with preparation for the next; also if the patient is already very happy at any intermediary stageStop. The patient and their satisfaction is what we are addressing not a topography chart.
In summary, practically any ocular situation (status post-cataract surgery, glaucoma surgery, retinal surgery, corneal transplant, trauma, chemical burns, etc.) provided it has visual potential and no ongoing or uncontrolled visually debilitating pathology can be addressed to achieve its best unaided visual capacity.
It is also very important to note here that the 20/20
we aim for in such cases is not the same as in a virgin |
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LASIK case where we are not pleased with 20/20 and |
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constantly strive to achieve 20/15 and 20/10. The |
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20/20 in these cases is qualitatively low (Gulani AC, |
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Ginsberg A., Quality of Vision and Optec 5000, March |
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2006). These are patients with poor/distorted vision |
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and becoming functional even with 20/40 (as refractive |
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surgeons we must always talk in terms of unaided vision) |
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is an ecstatic, life-changing outcome. Especially if you |
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consider that these techniques are all brief/topical/ |
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aesthetically pleasing and therefore a fond memory |
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for the patients. |
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As long as there is no intraocular pathology or |
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disease, i.e. retinal / neurological / uncontrolled |
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glaucoma, etc.; there is no reason why we cannot stage |
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towards a perfected visual outcome. The ability to help |
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patients with refractive surgical complications/ previous |
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surgeries/chemical burns/trauma/ etc. towards 20/20 |
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vision is no longer out of reach in aspirations or |
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outcomes. |
MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
Figure 11.2: In cases of Keratoconus, besides Shape the factor affected could also be Strength. When the corneal thickness is still above 350 microns we can put synthetic inserts like INTACS.
Assymetric, On-Axis INTACS for Keratoconus and PMD
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Figure 11.3: Conditions |
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wherein the Amniotic graft |
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was used to correct ocular |
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surface problems and |
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also extended to heal the |
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corneal defects asso- |
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ciated with them (i.e. |
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Extensive pterygium with |
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central corneal involve- |
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ment). Thus correcting the |
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Site, Sight, Strength and |
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Scar. This was followed |
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by excimer laser ablation |
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for achieving the desired |
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Shape for unaided emme- |
tropia |
ADVANCES IN CORNEOPLASTIQUETM: ART OF LASER VISION SURGERY
Figure 11.4: These are cases of anterior supraBowman scars. The
Sight and Strength being good, we can peel these scars under the excimer laser followed by simultaneous refractive ablation leading to correction of Scar (Unclear Cornea), Shape (Ammetropia) and Site (Central)
Figure 11.5: Patient |
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who |
had |
Aphakic |
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d e c e n |
t e r e d |
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E p i k e r a t o p h a k i a |
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nearly two decades |
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ago with best corrected |
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20/20 vision. Stage I: |
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Removal of her epi- |
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Lenticle (Correction of |
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Site, Scar, Shape and |
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Strength). This was |
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followed by placement |
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of |
secondary IOL |
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(Sight) to uncorrected |
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vision 20/25 |
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
Figure 11.6: Posteior corneal transplant (DSEK, DSAEK , KeyHole) for a case of Pseudophakic Bullous keratopathy. We have thus corrected the Site, Scar, Strength and Sight. This was followed by excimer laser surgery to correct the Shape
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Figure 11.7: Various forms |
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of lamellar corneal repairs |
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to build the cornea in |
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preparation for |
the final |
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S(Shape) with the excimer |
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laser. These repairs could |
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be anterior |
lamellar |
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(Sutureless or sutured) or |
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posterior (Sutureless-Key |
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Hole) transplants |
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ADVANCES IN CORNEOPLASTIQUETM: ART OF LASER VISION SURGERY
I use the Pentacam in my practice routinely (Gulani AC, Pentacam in Full Spectrum Refractive Surgery: Advanced Corneal Topography CourseAAO, Las Vegas 2006) and find it to be an essential tool towards a synergistic planned approach towards achieving emmetropia. This coupled with imaging techniques (ReSeevit Software and CSO imaging systems) provides intricate details for surgical planning.
With numerous refractive surgical modalities available today (refs 3 and 4) and also the new combinations of surgeries that we are seeing in their infancy (Cataract surgery post-LASIK, etc.) I believe diagnostic technologies will need surgeons to guide them through the waters of innovation as our
understanding and demands have surely increased and so have patient expectations.
REFERENCES
1.Gulani AC. “Lasik Corneal Complications: A New Stratified Classification”. Ophthalmology 1999;106:1457-58.
2.Gulani AC. “A New Concept for Refractive Surgery: Corneoplastique”. Ophthalmology Management 2006;57-63.
3.Gulani AC, Wang M. Future of Corneal Topography. Textbook of Corneal Topography in the Wavefront Era. Slack Inc 2006;26:303-04.
4.Gulani AC, L Probst. “ CONS of PRESBYOPIC LASIK”. In: LASIK: Advances, Controversies and Custom. Slack Inc (2004) 32B;367-69.
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