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Corneal cross-linking (CXL) is a procedure that stiffens the cornea by using riboflavin and ultraviolet (UV) light to create cross-links between collagen fibres.
CXL is the standard of care for ectatic conditions such as keratoconus, but it has also been used to treat pseudophakic bullous keratopathy (PBK) and other forms of corneal edema.
Standard CXL therapy involves debridement of the corneal epithelium and instillation of riboflavin followed by exposure of the central 7 mm of the cornea to ultraviolet A (UVA) light.
Unfortunately, this can result in complications such as stromal haze, scarring, corneal melting, infection, and limbal stem cell loss if decentred peripherally.
Cross-linking damages corneal nerves inducing loss of corneal sensation and dry eye. For patients who have isolated corneal edema, these complications could be minimized by applying CXL only to the affected area and leaving the remaining healthy cornea untreated. Thus, we describe a novel technique of applying focal CXL (FCXL) to treat localized PBK in a patient after Descemet membrane stripping automated endothelial keratoplasty (DSAEK).
A 67-year-old female patient presented with corneal edema and a visual acuity of counting fingers secondary to complications from intraocular lens dislocation and repositioning. Because of persistent corneal edema, with a corneal thickness of 720 µm, a DSAEK corneal transplant was performed. Successful attachment was achieved but with delayed re-epithelialization. Eight months postoperatively, the central cornea was clear, but the patient had persistent painful peripheral bullae inferiorly, with no improvement after Muro 128, prednisolone acetate 1%, or epithelial debridement and bandage contact lens (Fig. 1A). FCXL was applied to provide symptomatic relief of the peripheral bullae.
Fig. 1Corneal assessment before and after focal cross-linking (FCXL) treatment. A, Pre-FCXL: painful bullae with focal epithelial defect, concentrated on the medial border of the cornea, peripheral to the attachment point of the DSAEK graft. Enhanced with fluorescein dye. B, Three weeks post-FCXL: resolution of painful bullae and epithelial defect with residual epithelial irregularity and punctate fluorescein staining.
A focal UVA protector was constructed in a sterile manner and assembled using a Chayet LASIK eye drain (BD Visitec), adhesive, surgical plastic drape, surgical marking pen, and a 15-degree blade (Fig. 2A). Under sterile conditions, a clear section of the surgical drape, typically fastened to the patient, was adhered to the Chayet LASIK eye drain. The clear portion was coloured with a surgical marker. A crescent blade was used to make an incision in the drape overlaying the centre of the Chayet drain that matched the shape of the peripheral corneal defect.
Fig. 2Description of materials and focal cross-linking procedure. A, Materials used included a Chayet LASIK eye drain (BD Visitec), surgical plastic drape, a surgical marking pen, and a 15-degree blade. B, Preparation of ultraviolet-A (UVA) shield. A clear section of the surgical drape was adhered to the Chayet LASIK drain and coloured with a surgical marker. A crescent blade was used to cut out the desired crescent shape in the drape overlaying the centre of the Chayet drain. B, Standard Dresden cross-linking protocol was used. Thirty minutes of UVA with isotonic riboflavin applied to the crescent-shaped area, using the template to shield the remaining clear cornea and limbus from UVA light
After the loose epithelium was denuded from the treatment area and the cornea saturated with isotonic riboflavin solution, the eye was irradiated for 30 minutes at 3 mW/cm2 while the custom UVA protector was placed over the eye. A crescent-shaped cutout of the opaque surgical drape allowed UVA exposure to be directed only to the peripheral nasal aspect of the left cornea (Fig. 2C).
At postoperative day 10, the patient no longer felt pain, but a residual epithelial defect remained. By postoperative week 3, the epithelial defect had resolved with resolution of bullae and only slight epithelial irregularity over the treatment area. The patient remained pain free with no peripheral bullae until postoperative month 6. When central corneal edema with decreased visual acuity was observed, it was deemed that the graft had slowly failed and a successful DSAEK graft was repeated.
Focal corneal edema can be treated by a number of techniques including hypertonic saline drops, epithelial debridement, and bandage contact lens placement. These techniques, although successful in some cases, may not be effective in more advanced edema as was evidenced in our case.
Collagen cross-linking can treat corneal edema by increasing corneal stiffness, with improved visual acuity and relief of pain seen in patients with PBK 1 to 6 months after the procedure.
This relief is thought to be due to a decrease in corneal sensitivity in the first 3–6 postoperative months, which gradually recovers and may lead to recurrence of pain in patients with unresolved PBK.
Our patient also received approximately 6 months of pain relief after 1 application of FCXL. In hindsight, her presentation of peripheral PBK was a sign of early graft failure, and FCXL was used to manage peripheral PBK and reduce discomfort while she awaited repeat corneal transplantation.
In addition to PBK, FCXL may also manage other focal corneal diseases, such as infectious keratitis. Although the findings are not universal, CXL has treated antibiotic-resistant corneal ulcers, through the presumed direct antimicrobial effect of UVA and the increased resistance of the cornea to enzymatic lysis.
Because ectasia is associated with corneal thinning, a number of patients with advanced keratoconus may be excluded because they do not meet the 400-µm safety criteria. FCXL may be used to avoid treating thin areas while still providing therapy to the rest of the cornea. This treatment could be particularly useful for patients with severe ectasia and no scarring who could be stabilized with FCXL and then fitted with a vaulted scleral contact lens, thus obviating the need for corneal transplantation.
There are cross-linking devices that provide automated FCXL but at significant cost, demonstrated by a case report of a customized UV system that can vary UV exposure across the cornea.
Toric Topographically customized transepithelial, pulsed, very high-fluence, higher energy and higher riboflavin concentration collagen cross-linking in keratoconus.
Our method is currently available to most ophthalmologists and uses low-cost, disposable surgical supplies. It can be customized to each individual patient to selectively target diseased cornea and decrease the radiation to healthy tissue, thereby reducing nerve loss, dry eye, scarring, and limbal stem cell damage.
We propose that FCXL can be used to manage peripheral PBK or as a temporizing measure until keratoplasty is performed. Although not studied in this case report, FCXL may also prove useful in treating other conditions such as infectious keratitis and in patients with severe ectasia who would otherwise not be candidates for standard CXL. Further study is needed to demonstrate the clinical efficacy of FCXL and its potential role in treating various corneal pathologies.
References
Sorkin N.
Varssano D.
Corneal collagen crosslinking: a systematic review.
Toric Topographically customized transepithelial, pulsed, very high-fluence, higher energy and higher riboflavin concentration collagen cross-linking in keratoconus.
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