Zembla Documentary on Lasik, Pain, and Suicidality

This Lasik documentary was created by investigative journalists in Holland. The language is mostly Dutch, with English subtitles. The documentary focuses on corneal neuropathic path after Lasik and the suicidality it creates. Dutch physician Dr. Michael Brouwer and other Lasik sufferers in Holland are interviewed, as is Dr. Edward Boshnick in the United States (see EyeFreedom.com). The investigators ask: Is the experience of pain after Lasik really uncommon? What are the consequences when it occurs? Also interviewed are Dr. David Barsook and Dr. Morris Waxler. Dr. Barsook is Director of the Pain and Imaging Neuroscience (P.A.I.N.) Group at Boston Children’s Hospital, MGH ,and McLean Hospital at Harvard University. Dr. Barsook maintains that corneal pain after Lasik follows an established model of neuropathic pain. Dr. Morris Waxler is the FDA's former chief research scientist on Lasik. Dr. Waxler maintains at his website HelpStopLasik.com that "The FDA does not want to admit that millions of people have now had a surgery that never should have been approved by its own rules. The FDA is now engaged in covering-up a scandal and an epidemic, and its own corrupt practices. This should be exposed, and LASIK should end." He revisits these conclusions in the video.

Scleral Lenses in the Treatment of Post-LASIK Ectasia and Superficial Neovascularization of Intrastromal Corneal Ring Segments

Objective: This case report aims to explore the use of scleral lenses for the treatment of ocular and visual complications in an adult patient presenting with post-LASIK (Laser-Assisted in situ Keratomileusis) ectasia in both eyes with cross-linking in the right eye and Intrastromal Corneal Ring Segments (ICRS; IN- tacs, Addition Technology, Fremont, California) in the left eye.

Methods: Following a comprehensive eye exam and specific testing for contact lens fitting, scleral lenses were fitted with success in both eyes and dispensed. Due to progressive fibrosis and neovascularization of the inferior ICRS in the left eye, the inferior ICRS was removed and scleral lenses were refit with success.

Results: Prescribed scleral lenses helped the patient achieve optimal visual correction (20/20) as well as ocular protection of the cornea.

Conclusion: Post-LASIK ectasia is a common finding among contact lens specialists today. When ICRS surgery is involved, the fitting of contact lenses may become more challenging. Scleral lenses offer a unique way of addressing many issues raised in this case report such as corneal neovascularization and ectasia. This lens modality may be considered for any other case involving irregular corneal curvature following surgery and reduced visual acuity.

Key Words: Ectasia, ICRS, scleral lenses, neovascularization

Introduction: In the summer of 2013, patient JV, a 38 year-old Hispanic male, was referred by a cornea specialist for a contact lens evaluation for the treatment of fluctuating and unstable vision in both eyes. He had undergone a LASIK (Laser-Assisted in situ Keratomileusis) procedure in 2001 and was then diagnosed with post-LASIK ectasia in both eyes for which he underwent cross-linking in the right eye and Intrastromal Corneal Ring Segments (ICRS; IN- tacs, Addition Technology, Fremont, California) surgery in the left eye 4 weeks and 2 months, respectively, prior to his initial presentation. Scleral lenses were ordered for the patient and significantly improved the vision, both objectively and more so subjectively. A successful fit was obtained on the right eye and the lens was dispensed. On the left eye, however, an adequate fit could not be obtained because there was progressive fibrovascular growth over the inferior temporal ICRS with lens touch and resulting fluorescein staining at every visit despite consequent steepening of the lens. Because the ICRS continued to protrude forwards and push on the scleral lens, the patient was referred back to the cornea specialist for evaluation. The latter agreed with the assessment and discussed the recurrent inflammation and potential infection due to the ICRS and planned to remove the inferior segment in the near future. Earlier this year, when the inferior segment was removed, the patient returned for a new contact lens fitting of the left eye. At this time, the patient is very satisfied with both the vision and comfort he has with the scleral lenses. Although he does have some residual neovascularization in the lower cornea, the lens provides an adequate vault over the surface and has succeeded in maintaining the corneal integrity.

Case Report: J.V., a 38 year-old Hispanic male presented to the Global Vision Rehabilitation Center for a contact lens fitting and evaluation. He was referred by a cornea specialist for poor and unstable vision in both eyes and difficulty driving at night due to halos and starbursts around lights. A review of his ocular history revealed LASIK in both eyes in 2001, ICRS surgery 2 months prior in the left eye and a cross-linking procedure in the right eye 4 weeks prior to this initial presentation. He was also wearing a PROKERA lens 3 weeks prior to presentationfor 4-5 days over his right eye following the cross-linking. He had no history of glaucoma or trauma and was not using any eye drops. He had no history of ocular disease in his family. He had not been diagnosed with any medical problems, was not taking any medications and had no allergies to drugs. Entering Acuities measured 20/40- in the right eye and 20/30 in the left eye with spectacle correction. His refraction measured OD: +2.25 -4.50 x 080 and OS: +2.75 -5.00 x 105. With this correction his acuities were 20/30 and 20/25, respectively, however the patient reported significant distortion of the letters. His pupils were equal, round and reactive to direct and consensual illumination and there was no afferent papillary defect in either eye. Confrontational visual fields were full to finger counting in both eyes and extra ocular motility was full in both eyes. Slit lamp examination revealed Intacs segments in place 2 mm above and below the pupil in the left eye with crystallized deposits around the ring segments. He had superficial stromal vascularization extending to and arborizing along the inferior ring segment at 3:00 with mild underlying haze. The patient had clean lids and lashes, white and quiet conjunctivas, flat irides and clear lenses OD, OS. There were no proptosis or lid abnormalities in either eye. Intraocular pressures by Goldmann applanation tonometry measured 13 mm Hg OU at 11:09 am using one drop 0.5% proparacaine hydrochloride ophthalmic solution. Upon dilated fundus examination (using one drop 1% tropicamide and 2.5% Phenylephrine OU), the cup to disc ratios were found to be 0.2 OD, OS. The neuroretinalrims were healthy and pink in both eyes. The maculae were clear and flat in both eyes and retinal vasculature was of normal course and caliber. There were no breaks in the retinal periphery. There was a flat nevus just superior to the arcade in the right eye, which was approximately 2/3 of a disc diameter.

After the glasses were prescribed, contact lenses were strongly recommended as the primary treatment for the ectactic corneas in both eyes with vascularized Intacs in the left eye. In this condition, the ocular surface must be protected to minimize the risk of erosion; contact lenses help maintain constant lubrication of the corneal surface, which allows for its restoration. A soft bandage does not provide a good outcome for visual correction on a highly irregular cornea. Small diameter rigid gas permeable (RGP) lenses can provide a better alternative to improve visual acuity but do not protect the ocular surface. In fact, these lenses can increase mechanical stress on an already altered cornea in this case. One of the ways to resolve this issue could be to consider a piggy-back system, which implies fitting a high oxygen permeability soft lens carrier on top of which a high permeability RGP lens is fitted. In that way, the soft carrier aims to protect the cornea while the RGP restores visual acuity. Another solution includes the implementation of hybrid lenses. These consist of a gas permeable rigid center surrounded by a silicone hydrogel soft skirt. In fitting this lens, the skirt is designed to lift the rigid center off the corneal surface so that it never has to interact with it. However, there have been some reported cases of warpage with these lenses.1 In addition, most of, if not all of the hybrid lenses do not offer enough oxygen permeability to maintain ocular health in the presence of a compromised cornea.1 Large diameter RGP lenses can also be considered. These designs have become more and more popular and are available in several options: a corneo-scleral lens (12.5 mm to 15 mm), supported partly by the cornea and partly by the sclera; a mini-scleral lens (15 mm to 18 mm) vaulting the cornea, supported by the fluid layer and the conjunctiva; or a larger scleral lens (18 mm to 25 mm) with the same fitting philosophy as the mini-scleral lens but with different parameters.2 They are fitted in a way to vault the cornea. They maintain a constant reservoir of fluid between the lens and the cornea to ensure that it remains lubricated. More over, this fluid layer also compensates for the surface irregularities, leading to improved visual acuity. This modality can provide the comfort of a soft lens with the optical quality of a gas permeable lens. In that way, large diameter RGP lens designs currently available are considered the best option to provide health benefits and increased comfort compared to smaller corneal RGP and, in this case, soft lenses. In the case of post-LASIK ectasia followed by cross-linking in one eye and ICRS in the other, in order to determine which type of large diameter RGP lens to use, any touch on the cornea should be avoided. Corneo-scleral lenses are contraindicated because a small portion of the cornea supports most of the weight of the lens. This may result in a stress to the tissue that could cause a corneal epithelial defect and/or generate scarring. Mini-scleral lenses represent an improved option, where cornea-lens touch is absent with a limited amount of fluid layer. In addition, they are smaller than the large scleral lenses and are therefore easier to handle and less intimidating for patients to insert into their eyes.2

The Jupiter lens was chosen initially with the following parameters: OD base curve: 43.05 D (7.84 mm), diameter: 16.60 mm, power -3.00 with a reverse geometry curve. Using the VisanteTM Anterior segment OCT, it was determined that there was excessive (300 microns) apical clearance between the back of the lens and the front surface of the cornea. The base curve was the flattened to 41.01 D (8.23 mm), diameter: 16.60 mm, power -1.00, over-refraction: +0.25 Visual acuity: 20/20. For the left eye, an initial base curve of 41.98 D (8.04 mm) was chosen and also determined to be too steep and was then flattened to 39.02 D (8.65 mm).The diameter was 16.60 mm and the power +1.00. An over-refraction of +0.50 was found with a visual acuity of 20/20. When adequate apical clearance was confirmed (150 - 200 microns) in both eyes (Figure 2), the lenses were ordered with the following parameters:

OD: diameter: 16.60 mm, base curve 41.00 D (8.23 mm) reverse curve, power -0.75

OS: diameter: 16.60 mm, base curve 39.00 D (8.65 mm) reverse curve, power +1.50.

Figure 2: Visante TM Anterior Segment images of the right (a) and left (b) eyes fitted adequately with a scleral lens. Note 150 - 200 microns of apical clearance between the corneal surface and back surface of the scleral lens. Not the Intacs represented by empty spaces in the left eye using enhanced high resolution imaging.

When the patient returned 2 days later for dispensing of the lens, anterior segment examination revealed identical findings to the previous visit. Both lenses provided adequate apical clearance, no blanching or vascular compression of the conjunctival vessels, visual acuity of 20/20 in both eyes and patient comfort in both eyes. Following appropriate training, the patient proved to be proficient with both insertion and removal of the lenses. RGP cleaner and conditioning solution (Boston™) were recommended. Non-preserved 0.9% NaCl inhalation solution was prescribed to fill the lens before insertion.

When the patient returned for follow-up 2 days later, the vision continued to be 20/20 in both eyes, however, the patient reported mild discomfort in the left eye, especially after lens removal. Using the VisanteTM Anterior segment OCT to assess lens clearance, the right eye was acceptable with a clearance of 150 µm. Conversely; the left eye had adequate clearance centrally of 100-110 µm but minimal touch over the superior ring segment. The tissue outgrowth over the inferior ring segment was more pronounced than the last visit with lens touch at this location. (Figure 3) When the left lens was removed, and fluorescein sodium instilled in the left eye, mild diffuse punctate epithelial erosions could be appreciated and there was positive staining at 4:00 over the inferior ring segment.

Figure 3. Visante Anterior Segment OCT enhanced high resolution imaging of the left eye showing outward growth of the cornea around the inferior ICRS toward the back surface of the lens with minimal clearance in that area. Note the adequate clearance in the rest of the cornea.

In order to adequately vault over the outgrowth of tissue inferiorly and try to reverse the staining, an 18.20 mm lens was selected with a base curve of 39.99 D (8.44 mm) with power: plano. Until the new lenses were dispensed, left lens wear was discontinued. At the dispensing visit, slit lamp examination of the left eye showed improvement of corneal integrity over the inferior ring segment from 3:00-6:00. While the right eye continued to have adequate apical clearance, some bearing was appreciated over the superior ring segment at 119° in the left eye. The patient was then scheduled to return in 1 week to monitor the left eye.

When the patient returned, he reported good vision and comfort in the right eye but continued to complain of mild discomfort in the left eye with lens wear and removal, though improved from the last visit. The visual acuity was stable as was the integrity of the right cornea. After slit lamp examination of the left eye, the patient was noted to have improvement and almost complete resolution of the previous punctate epithelial erosions and irritation over the inferior ring segment. The mild discomfort experienced by the patient was attributed to a larger diameter lens in the left eye and therefore increased lens awareness. The patient was educated on lens awareness and that adequate adaptation time would be needed in order to tolerate the lenses. The patient was then scheduled for follow-up in 1 month. At this visit, the patient reported pain after lens removal in the left eye. Slit lamp and VisanteTM Anterior segment OCT examination both showed the inferior corneal ring segment pushing anteriorly at 6:00 against the scleral lens (Figure 4) with positive staining in this area of the cornea. Lens wear was discontinued, Tobradex was prescribed every hour and the patient was to return the following day. The next day, the patient reported improvement but still had positive staining in the same area of the cornea. Tobradex ointment was prescribed every 2 hours in the left eye on the first day and every 4 hours in the left eye on the second day.

Figure 4. Visante Anterior Segment OCT enhanced anterior segment imaging of the left eye showing outward growth of the cornea around the inferior ICRS toward the back surface of the lens with minimal clearance in that area. Note the adequate clearance in the rest of the cornea.

Three days later, at the follow-up, the staining had mostly resolved. Because the fibrovascular growth around the inferior corneal ring segment seemed to be progressing, the patient was referred for evaluation to a cornea specialist at the Bascom Palmer Eye Institute. The latter agreed with the prior assessment of fibrosis or infiltration of the inferior ring segment with outward protrusion in addition to neovascularization in the lower half of the cornea. He discussed with the patient the recurrent inflammation and potential infection due to the Intacs and decided to proceed with removal of the inferior ICRS. Antibiotics were continued and cultures obtained for the left eye.

Two months later the inferior corneal ring was explanted. Cultures and pathology were negative and the patient was prescribed PredForte 6 times a day and Vigamox 4 times a day. The steroid drops were progressively tapered and at the final follow-up with the surgeon, the latter reported that the cornea had healed nicely in the area of explantation with no staining. The antibiotic drop was discontinued and PreForte was maintained at 4 times a day for 1 month and then slowly tapered afterwards. The patient was then referred back to the Global Vision Rehabilitation Center for a new contact lens fitting. A new scleral lens was fit on the left eye. For this lens, a diameter of 20.60 mm was chosen in order to completely vault over the cornea, the limbus and perilimbal bulbar conjunctiva. A base curve of 8.39 mm and plano power was chosen. When the lens was dispensed, the superior corneal ring segment was touching the back of the lens, so the latter was steepened by 60µm. The patient is now wearing a 20.60 mm diameter lens with a base curve of 8.23 mm, reverse curve and a power of -1.50. The vision continues to be 20/20 in both eyes with no distortion. There is adequate apical clearance and comfort in both eyes. (Figure 5) Although the patient continues to have neovascularization on the inferior portion of the cornea in the left eye, what was thought to have been the insult was removed; the patient is expected to improve and is being monitored closely.

Figure 5. Visante Anterior Segment OCT enhanced high resolution imaging of the left eye showing 150 - 200 microns of apical clearance. Note the absence of inferior ICR and mild scarring in the area of explantation.

Differential Diagnosis:

Ring segment Extrusion

The most common cause of ICRS explantation; 48.2% according to a study by Ferrer and associates.3 This is caused by the superficial part of the corneal stromathinning over time, causing the ring segment to protrude forward leading to an epithelial breakdown. The latter is a necessary finding in order to make a diagnosis of ring segment extrusion.3In most cases, extrusion is accompanied by melting; vascularization also occurs in some cases.3The patient discussed in this case had corneal staining, indicating an epithelial break. However the cause of the irritation was not stromal thinning but by the superficial cornea protruding forward and rubbing on the scleral lens. This is evident when the scleral lens is discontinued at one visit and steepened at a later visit; the patient experienced almost complete resolution of the corneal staining. If the epithelial break had been caused by a lack of stromal integrity, the epithelium would not have healed by discontinuing contact lens wear or improving the fit. In order to give this patient adequate vision, a scleral lens was deemed necessary. Because an adequate fit could not be obtained with a scleral lens due to superficial neovascularization and fibrosis of the ICRS, the patient was referred for an explantation evaluation.

Corneal Neovascularization

Infectious Keratitis

This is one of the four leading causes of ICRS explantation.3 In order to make this a definitive diagnosis, cultures must be positive.3 In the case reported here, preoperative cultures and pathology of the corneal epithelium as well as post-operative cultures and pathology of the Intacs were both negative, rejecting microbial keratitis as a potential diagnosis.

Mild channel deposits around the ICRS

These channel deposits, made up of cells and protein, are usually found on the proximal end of the ring segment, near the incision.3Ruckofer et al. suggest that the deposits are caused by the physical separation of stromal lamellae when they are opened to create a channel for implantation of ICRS.4 They also reported that the incidence and density of deposits increase with segment thickness and duration of implantation. Although they report an incidence as high as 60%4, no deposits could be seen on clinical examination or using the VisanteTM Anterior Segment OCT in the patient described here.

Segment migration

This post-operative complication causes undesirable refractive outcomes.5The patient discussed in this case had no refractive complaints and stable vision with the help of scleral lenses. Segment migration has not been shown to cause discomfort similar to that experience by this patient.5 In addition, his topography was stable from the time we first saw him until his referral back to the surgeon, further confirming the stability of the segments’ position.

Corneal melting

This is one of the four leading causes of ICRS explantation.3Given the fact that the patient’s corneal staining was completely resolved following the discontinuation of scleral lens wear, corneal melting was not the causative factor here. The insult was the superficial cornea protruding forward and rubbing on the scleral lens. This is evident when the scleral lens is discontinued at one visit and steepened at a later visit; the patient experienced almost complete resolution of the corneal staining. If the epithelial break had been caused by a lack of corneal integrity, the epithelium would not have healed by discontinuing contact lens wear or improving the fit. In cases of corneal melting, the epithelium begins to breakdown, followed by stromal loss.3 The patient reported here had no stromal loss, as confirmed by the VisanteTM Anterior Segment OCT and slit lamp examination. In order to give this patient adequate vision, a scleral lens was deemed necessary. Because an adequate fit could not be obtained with a scleral lens due to superficial neovascularization and fibrosis of the ICRS, the patient was referred for an explantation evaluation.

Discussion

The patient reported here had superficial corneal neovascularization after implantation with ICRS. ICRS is said to be promising, minimally invasive and reversible refractive treatment for the management of low to moderate myopia, keratoconus and post-LASIK ectasia.3,6,7 It was intended to achieve a clear central optical zone and preserve corneal tissue and defer corneal transplant surgery8. The rings are made of Polymethylmethacrylate (PMMA) in the shape of sections of a circumference and are inserted in a semicircular channel between the lamellae of the stroma. The 3 main ICRS on the market are Intacs (Addition Technology, Inc.), Ferrara (Ferrara Ophthalmics Ltd.), and Keraring (Mediphacos Ltd.).3 The changes induced in corneal curvature can be predicted using Barraquer’s Law; when a material is added to the periphery of the cornea, a flattening effect is achieved. 9 ICRS improve distance visual acuity, cylinder, and coma-like aberrations in post-LASIK ectasia10, but the indications for ICRS implantationfor this condition remain unclear.11 In a case series done by Brenner et al, the best candidates for ICRS in patients with post-LASIK ectasia were those who lost two or more lines of best corrected visual acuity because of ectasia and patients with grade 4 post-LASIK ectasia, defined as severe visual debilitation and a best corrected visual acuity less than 20/40.10 These patient showed a mean improvement of 2.89 lines of visual acuity 12 months after ICRS implantation. Furthermore, those who had grade 2 and 3 ectasia gained little acuity with implantation whereas those who had grade 1 ectasia experience loss of visual acuity after implantation.10

Intrastromal corneal ring segment implantation has been associated with intraoperative and postoperative complications.3 Intraoperative complications include segment decentration,12ICRS asymmetry,12inadequate channel depth,12superficial channel dissection with anterior Bowman layer perforation,3and anterior chamber perforation.3Although ICRS are usually well tolerated, some in vitro studies found activation of keratocytes, accumulation of lipids in cells and new collagen formation after implantation.13 Several postoperative complications have been described, including ring segment extrusion,3,12corneal neovascularization,3,6,12infectious keratitis,3,12mild channel deposits around the ICRS,3segment migration,3,12and corneal melting.3In the U.S. Food and Drug Administration phases II and III clinical trials, for Intacs, segment removal was necessary in 4.68% of eyes.8 The authors of this study concluded that intrastromal ring segments were safely, effectively, and easily removed, with a return to preoperative refractive status within 3 months.8

Corneal neovascularization after Intacs has not been frequently reported6,14; it is usually superficial and localized to the site of the surgical wound.6In a study of 33 eyes with keratoconus that underwent Intac surgery, Siganos and associatesfound superficial, mild vascularization at the wound site in 1 eye after 2 months.15Kymionis and associatesdescribed similar findings in 2 of 10 eyes treated with Intacs for post-LASIK ectasia.16 Both Al-Torbak et al and Cosar et al reported cases of deeper vascularization noticed 7 months and 3 years after surgery, respectively.6,14Cosar speculates that hypoxia of the cornea superficial to the Intacs may be the triggering factor for neovascularization as no inflammation was found on clinical examination14. Both Al-Torbaket al and Cosar et al report disappearance of the vessels after treatment with explantation of the Intacs and anti-inflammatory therapy, suggesting that the Intacs incited the neovascularization.6,14

If the causative factor is not removed, it is safe to assume that the neovascularization may continue to progress. Although a scleral lens is a good indication for the visual correction of a post-LASIK ectasia cornea with ICRS, if the neovascularization and firbovascular growth progresses, no scleral lens can be adequately fit. Therefore ICRS explantation would be necessary. In order to achieve adequate visual acuity, the patient would need to be refitted post-surgically.

Conclusion:

In the patient reported here, a scleral lens fitting, necessary to achieve adequate visual acuity, could not be executed with success on the left eye until ICRS removal was completed. The patient’s inferior ICRS was causing hypoxia in the lower cornea, inducing superficial neovascularization and outward fibrovascular proliferation, causing corneal epithelial breakdown when a scleral lens was being worn and moderate to severe discomfort. Following inferior ICRS explantation, a scleral lens was successfully fit and the patient satisfied. In addition, the neovascularization is expected to regress because the insult is now removed. It was extremely rewarding to use these lenses and thereby provide clear vision to a patient who had been struggling with poor and unstable vision following his LASIK procedures. Although fitting a scleral lens on an eye with ICRS complications did not come without its challenges, following appropriate evaluation and treatment by an outside cornea specialist, adequate vision and comfort was achieved.

With the increasing recent interest of clinicians and manufacturers, scleral lenses are becoming far more “mainstream” in contact lens practice. As optometrists, we should strive to continuously update our expertise in the area of contact lens design, thereby providing our patients with the latest lens technology and best solution for their signs and symptoms.

1)

Gardner D, Zimmerman A. Myopic shift secondary to hybrid lens wear. Contact Lens Spectrum. 2012 Jun;27: 44-48.

2)

Van der Worp, EA Guide to Scleral Lens Fitting. [Forest Grove, Ore.]: [College of Optometry, Pacific University], 2010: 1-4.

3)

Causes of intrastromal corneal ring segment explantation: Clinicopathologic correlation analysis

4)

Ruckhofer J, Twa MD, Schanzlin DJ. Clinical characteristics of lamellar channel deposits after implantation of intacs. J Cataract Refract Surg 2000; 26:1473–1479

5)

Intracorneal Ring Segment Explantation After Intracorneal Ring Segment Implantation Combined With Same-Day Corneal Collagen Crosslinking in Keratoconus

6)

Al-Torbak A, Al-Amri A, Wagoner MD. Deep corneal neovascularization after implantation with intrastromal corneal ring segments. Am J Ophthalmol 2005; 140: 926-7.

7)

Clinical outcomes after intrastromal corneal ring segments reoperation in keratoconus patients

8)

http://www.accessdata.fda.gov/cdrh_docs/pdf4/h040002b.pdf

9)

Changes in Anterior and Posterior Corneal Parameters in Patients with Keratoconus After Intrastromal Corneal-ring Segment Implantation

10)

Brenner LF, Alio JL, Vega-Estrada A, et al. Indications for intrastromal corneal &ring segments in ectasia after laser in situ keratomileusis. J Cataract Refract

Surg 2012; 38:2117 – 2124.

11)

Evolution in the use of intrastromal corneal ring segments for corneal ectasia

12)

Miranda D, Sartori M, Francesconi C, Allemann N, Ferrara P, Campos M. Ferrara intrastromal corneal ring segments for severe keratoconus. J Refract Surg 2003; 19:645–653

13)

Twa MD, Ruckhofer J, Kash RL, et al. Histologic evaluation of corneal stroma in rabbits after intrastromal corneal ring implantation. Cornea 2003;22:146–152.

14)

Late onset of deep corneal vascularization: a rare complication of intrastromal corneal ring segments for keratoconus

15)

Siganos CS, Kymionis GD, Kartakis N, et al. Management of keratoconus with Intacs. Am J Ophthalmol 2003;135:64–70.

16)

Kymionis GD, Siganos CS, Kounis G, et al. Management of post-LASIK corneal ectasia with Intacs inserts. Arch Oph- thalmol 2003;121:322–326.

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