All of us Vs Keratoconus


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Post Info TOPIC: Other Types of Crosslining


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Date: Wed May 27 5:28 PM, 2020
Other Types of Crosslining
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I wanted to know if there is in this current times or in the pipeline other forms of Crosslinking?   



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Date: Wed May 27 7:21 PM, 2020
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With the study data added at the end, one relatively new development in collagen cross-linking technology is a method that uses green light to activate rose bengal, a well-known diagnostic agent for ocular surface damage. This technology has already proven useful in sealing cornea wounds, bonding amniotic membrane to the corneal surface, and for applications in many other tissues [1-6].

Photochemical cross-linking of the corneal stroma using rose bengal and green light (a process referred to as RGX) has been shown to produce a similar increase in rabbit corneal stiffness to that achieved with riboflavin/UVA cross-linking. However, in contrast to riboflavin/UVA cross-linking which causes apoptotic cell death at depths up to 350 µm, RGX is limited to the anterior 100 µm of the tissue and is non-toxic to stromal keratocytes [7, 8]. 

Reconstructed bio-mechanical parameters from numerical finite element simulations show that the cross-linked layer of the cornea is actually stiffer after RGX than after riboflavin/UVA cross-linking.

 

However, the cross-linked layer is substantially thinner after RGX and air puff deformation imaging of rabbit eyes indicate that the overall corneal stiffening effect achieved with RGX does not match that of riboflavin/UVA cross-linking [9].

 

Preliminary studies on rabbit corneas indicate that RGX has the potential to offer a rapid (less than 15 min), safe and effective treatment for ectatic diseases but further studies are needed to assess its safety in terms of the retina and iris.

 

[1] Gu, C. et al. Photochemical tissue bonding: a potential strategy for treating limbal stem cell deficiency. Lasers Surg Med. 2011 43(5):433-42.

[2] Henry, F. P. et al. Real-time in vivo assessment of the nerve microenvironment with coherent anti-Stokes Raman scattering microscopy. Plast Reconstr Surg. 2009;123(2 Suppl):123S-30S.

[3] O’Neill, A. C. et al. Microvascular anastomosis using a photochemical tissue bonding technique. Lasers Surg Med. 2007;39(9):716-22.

[4] Proańo, C. E. et al. Photochemical keratodesmos for bonding corneal incisions.Invest Ophthalmol Vis Sci. 2004;45(7):2177-81.

[5] Tsao, S. et al. Light-activated tissue bonding for excisional wound closure: a split-lesion clinical trial. Br J Dermatol. 2012;166(3):555-63.

[6] Verter, E. E. et al. Light-initiated bonding of amniotic membrane to cornea. Invest Ophthalmol Vis Sci. 2011;52(13):9470-7.

[7] Cherfan, D. et al. Collagen cross-linking using rose bengal and green light to increase corneal stiffness. Invest Ophthalmol Vis Sci. 2013;54(5):3426-33.

[8] Zhu, H. et al. Corneal crosslinking with rose Bengal and green light: efficacy and safety evaluation. Cornea. 2016. Epub ahead of print.

[9] Bekesi, N et al. Corneal biomechanical response following collagen cross-linking with rose bengal-green light and riboflavin-UVA. Invest Ophthalmol Vis Sci. 2016;57(5):992-1001.

 



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Date: Thu May 28 3:16 AM, 2020
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Thanks for exaplaining Sven. Well it looks like the genie is (well and truly) out of the lamp!



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Date: Thu May 28 3:22 AM, 2020
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I haven't finished on this topic yet!

Pharmacologic alternatives to the standard corneal cross-linking procedure, which avoid the need for epithelial debridement and irradiation and can be used to treat all corneas irrespective of thickness, are currently being investigated.  In vitro studies on porcine eyes have shown that aliphatic -Nitro alcohols act as both formaldehyde and nitrite donors under physiologic pH and temperature to induce crosslinking [1-2] and are capable of inducing cross-links in the cornea with negligible effects on light transmission [1].

The preliminary results suggest that such compounds could be used as topical stiffening agents for Keratoconus and related disorders [1]. However, their precise mechanism of action is currently unclear and a better understanding of the specific chemistry involved is crucial to enhancing the speed and efficiency of the cross-linking effect.

 

[1] Paik, D. C. et al. Initial studies using aliphatic beta-nitro alcohols for therapeutic corneal cross-linking. Invest Ophthalmol Vis Sci. 2009;50(3):1098-105.

[2] Paik, D. C. et al. Aliphatic beta-nitro alcohols for therapeutic corneal cross-linking: chemical mechanisms and higher order nitroalcohols. Invest Ophthalmol Vis Sci. 2010;51(2):836-843.



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Date: Thu May 28 7:17 PM, 2020
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Constant optimization goes on in treatment options where ever possible. With what works so far and approved by the FDA in regards to CXL it is concidered that adding further oxygen will help. This article goes in to it in more detail: https://www.ophthalmologytimes.com/surgery/traversing-cxl-pathway-where-do-we-go-here



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Date: Thu May 28 11:53 PM, 2020
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This has been an interesting mini-series! (I am adding references again so you may do further reading)

Although effective in the management of keratoconus, the standard riboflavin/UVA collagen cross-linking procedure has several drawbacks, including a lengthy treatment time and a prolonged exposure to UV irradiation which is harmful to the keratocytes (cells) within the tissue [1,2]. As a result, researchers have also been investigating the potential of alternative corneal stiffening treatments that do not require UVA exposure.

One possibility is photochemical corneal stiffening by topical application of a novel photosensitizer referred to as WST11 followed by exposure to non-hazardous, near infrared (NIR, 755nm) light [3]. WST11, or  palladium bacteriochlorin 130-(2-sulfoethyl) amide dipotassium salt,  is a synthesized chemical derivative of a photosynthetic pigment that generates oxygen radicals (O2– and •OH) after illumination with NIR [4,5]. One role of these photogenerated radicals is thought to be the promotion of protein cross-linking [6].

The treatment of rabbit corneas with WST11/NIR has been shown to increase corneal biomechanical strength without generating singlet oxygen in the cornea [3]. When the WST11 was formulated with dextran T500 (WST-D) the treatment again resulted in significant corneal stiffening but also resulted in a reduction in post-treatment oedema and faster epithelial healing [3].

 

[1] Wollensak, G. et al. Keratocyte cytotoxicity of riboflavin/UVA-treatment in vitro. Eye. 2004;18:718–722.

[2] Wollensak, G. Histological changes in human cornea after cross-linking with riboflavin and ultraviolet A [letter]. Acta Ophthalmol. 2010;88:e17–e18.

[3] Marcovich, A. L. et al. Stiffening of rabbit corneas by the bacteriochlorophyll derivative WST11 using near infrared light. Invest Ophthalmol Vis Sci. 2012;53:6378-88.

[4] Ashur, I. et al. Photocatalytic generation of oxygen radicals by the water-soluble bacteriochlorophyll derivative WST11, noncovalently bound to serum albumin. J Phys Chem. 2009;113:8027–8037.

[5] Mazor, O. et al. WST11, a novel water soluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution, and vascular targeted photodynamic activity against melanoma tumors. Photochem Photobiol. 2005;81:342–345.

[6] Liu, K. et al. Superoxide, hydrogen peroxide and hydroxyl radical in D1/D2/cytochrome b-559 Photosystem II reaction center complex. Photosynth Res. 2004;81:41–47.



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Date: Sun May 31 4:20 PM, 2020
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The term which comes to mind is - Tour De Force !



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