Take Off Again Afrter Linking Djo

Corneal Collagen Crosslinking for Keratoconus: An update

Yogita Gupta

Dr. Rajendra Prasad Heart for Ophthalmic Sciences, All India Found of Medical Sciences, New Delhi, India

Corresponding Writer:

Yogita Gupta

Dr. Rajendra Prasad Middle for

Ophthalmic Sciences, AIIMS, Delhi, India

Email id: yogitagupta30@gmail.com

Published Online: 26-JUL-2017

Abstract

Keywords :

Collagen cantankerous-linking (CXL) is a bioengineering technique to increase the mechanical stability of the cornea in corneal ectatic disorders such as keratoconus (KC). Recently, U.S. Nutrient and Drug Administration (FDA) gave approving in April 2016 to Avedro™ Inc.'s CXL system to care for patients with progressive KC and post-LASIK ectasia.

Historical aspects: CXL was first performed in creature eyes in the 1990s at Dresden University, Germany ^one by Profs. Theo Seiler and Eberhard Spoerl, who found a significant increment in corneal biomechanical stiffness by combined riboflavin (RF)/ultravoilet-A (UVA) treatment (Epithelium-off Dresden protocol). Its clinical usefulness for halting the progression of KC was first demonstrated by Wollensak et al ^two in 2003. In the final few years, various studies have shown that CXL is effective in slowing the progression of KC. ^{two- 7}

Mechanism of Action: Normal corneal stroma has collagen fibrils with bridges/ cross links present betwixt them. Keratoconic corneas have distorted system of these collagen fibrils, with reduced number and tensile force. Riboflavin (Vitamin B2), undergoes excitation and photo activation by ultraviolet (370 nm) irradiation and produces reactive oxygen radicals that crusade induction of intrahelical and interhelical collagen crosslinks by forming new covalent bonds. This increases corneal rigidity by 330% ¹ and stiffens the anterior corneal stroma.

Function in KC: Pediatric and boyish cases of KC evidence an accelerated progression (88%5 of optics) as compared to adults. CXL is now an established treatment option for such progressive cases of KC. Currently followed international guidelines described at the 7th International CXL Meeting (www.cxl-congress.com) at Milan in 2011 are: CXL is indicated in any patient younger than 27 years with ectatic disease, while patient older than 27 years can be monitored for signs of progression most commonly defined as ⁸ :

Increase of 1 D of maximum 1000-reading (Kmax) or increase of manifest cylinder and/or deterioration of corrected altitude visual vigil (CDVA) within 1 twelvemonth AND contact-lens-dioptric changes which require replacement every 2 years or less.

The criteria of "progression" followed in various studies (Tabular array 1) however require validation.

Contraindications: Age<eight years, significant or nursing mothers, corneal thickness(CT) <300-350 µm (to prevent endothelial toxicity in thinner corneas), astringent central corneal scarring, severe ocular surface disease, astringent immunosuppression, collagen vascular disease, poor epithelial healing and RF allergy are the usual contraindications.

Technique: According to patient'due south age, mental state and co¬operation ability, either general or topical anesthesia can be utilized. The CXL procedure (Dresden protocol) involves:

• Step i: Epithelial debridement (around eight mm zone)

• Step two: Isotonic RF (0.ane% riboflavin in  20% Dextran T500) instillation for 30 minutes; one drop every 2-3 minutes

• Step 3: UV A exposure (30 minutes; 365 nm; 3mW/cm2) along with RF instillation

A bandage contact lens (BCL) is placed at the end.

Postoperative Regime: Followup examinations are done on 24-hour interval 1, Day iv, Week ane, and then monthly for upto three months, three-mothly upto one year and six-monthly thereafter.

Medications include: Topical moxifloxacin hydrochloride drops TDS for one week, topical carboxymethylcellulose sodium drops QID for 1 month. BCL is removed later on complete epithelialization (commonly fourth day). Topical fluorometholone center drops are started after complete epithelialization: QID for one month, tapered thereafter over ii weeks. Oral analgesics are given, if required.

Treatment Protocols and Modifications: Encouraged by the success of conventional CXL, other modifications similar accelerated CXL (ACXL), hyposmolar CXL and transepithelial CXL (TECXL) are too being performed for KC.

• Conventional CXL (CCXL)/ 'Dresden Protocol'

- Epithelium-off

- UVA with 3mW/cm2 radiations X thirty mins

- Total energy dose: 5.4J/cm2

• Accelerated CXL (ACXL)13

       - Epithelium-off

       - 15 mins RF + UVA : nine min x 10 mW/cm2 or 5 min 10 18mW/ cm2 or 15 min x 6mW/cm2 (product of two numbers remains xc)

       - Total free energy dose: 5.four J/cm2

       - Based on Bunsen-Roscoe law of reciprocity (the result of a photochemical reaction is directly proportional to total irradiation dose irrespective of time)

       - Less surgical time, increased patient comfort with comparable results as proven past a randomized controlled trial. ^fourteen

       - Conjectured that compliance is amend, peculiarly in children

       - Avedro KXL™ Organization (Avedro, Waltham, Mass., USA) (Figure 1) uses this protocol.

• Transepithelial CXL (TECXL)

- Epithelium-on

- UVA with 3mW/cm2 radiation X xxx mins

- Total energy dose: 5.4J/cm2

- Chemical methods: Utilise of special 0.ane% RF solution used (with dextran 15.0%, trometamol and EDTA), benzalkonium, tetracaine, ethanol, etc.

- Mechanical methods: Grid like epithelium removal, microabrasions, excimer laser-assissted epithelium removal, femto pocket, iontophoresis, etc.

- Less patient discomfort: less (i/5th) efficacious ^xv than epi-off CXL

• Pulsed Light ACXL ^sixteen :

- Optimized intraoperative oxygen availability improving functional outcomes compared with continuous like treatment

- Epithelium-off

- one second on/1 second off of UVA exposure followed

- Deeper stromal penetration

• Hypo-osmolar CXL

- Used if CT is 350-400 µm

- Use of 0.5% RF with 0.9% sodium chloride solution, followed by UVA exposure

- Intraoperatively, CT measured and RF instillation repeated till the minimum CT reaches 400 µm

• Contact Lens Assissted CXL ¹⁷

- Utilize of RF-soaked BCL of negligible ability to artificially increase the corneal thickness for CXL

- Efficacy still to exist priven

• Customised Debridement: Epithelial Island CXL ¹⁸

- Cone noon region is left intact (epithelial island) with selective epithelial debridement of paracentral region (ep-off island)

• CXL Plus Procedures

- Simultaneous topography-guided procedure like PRK (photorefractive keratectomy)

- Thermal keratoplasty procedures (e.thousand. Keraflex)

- INTACS (Intrastromal corneal band segments)

- Lasik Xtra

• PACK-CXL ^nineteen

      - Photoactivated chromophore for infectious keratitis –CXL

      - Culling to standard antibiotic therapy in treating infectious corneal disorders

       - May help reduce brunt of microbial resistance

Complications of CXL: Corneal brume (90%), sterile infiltrates (7-10%) and corneal edema (specially in sparse corneas) are common complications. There tin can be continued progression of KC. Infective keratitis, reactivation of herpes simplex virus infection and endothelial cell loss are rarely seen.

Nevertheless, the current stand up in clinical practice remains that CXL is a safe and efficacious handling modality for corneal ectatic diseases and holds hope for arresting their progression.

References

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2. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135:620–7.
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13. Kymionis GD, Tsoulnaras KI, Liakopoulos DA, Skatharoudi CA, Grentzelos MA, et al. Corneal Stromal Demarcation Line Depth Post-obit Standard and a Modified High Intensity Corneal Cross-linking Protocol. J Refract Surg 2016; 32:218–22.
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