Research and Innovation
A £1.37 Million MRC Award To Develop A Pre-Medicated Synthetic Human Corneal Equivalent To Treat Corneal Blindness
- (March 2020)

Corneal disease is a major cause of blindness world wide and transplantation with a human donor cornea remains the main clinical line of therapy. However, the demand for corneal donation outpaces the supply, leading to delayed visual rehabilitation for several hundreds of patients worldwide who are awaiting corneal transplantation. Furthermore, conventional corneal transplants has a high risk of failure in patients with severe ocular surface disease and vascularised cornea often necessitating repeated transplant procedures without much visual success. A recent UK graft registry assessment showed up to 50% of patients requiring a full thickness corneal transplant (PK) had such high risk characteristics with poor prognosis with conventional corneal transplantation. A synthetic cornea could offer the necessary solution for these patients and remains an unmet need in this field. In response to our project grant application in March 2020, the Medical Research Council (MRC) awarded a £1.37m for this project as a career development grant to Dr Hirak K Patra, University of Cambridge and University college London in collaboration with Prof Madhavan Rajan at Addenbrooke’s Hospital and Anglia Ruskin University, Cambridge to develop a Assisted Regeneration Artificial Cornea (ARCs) which will mimic biological properties of the human cornea and have additional function as a mediated device with theranostic potential. Overseas collaboration with University of Montreal, Canada and Harvard, United States, would bring international expertise to our project. This combined diagnosis and therapeutic approach will enable disease monitoring and treatment to severe corneal scarring disorders for the first time and promises to address the unmet need in the field for artificial cornea.

  1. Femtosecond lasers for advanced corneal and cataract surgery at Addenbrookes Cambridge Eye Unit

    Laser technology enables surgeons to operate with greater precision when compared to conventional surgery. Addenbrooke’s Hospital is the first NHS unit in the UK to install the state-of-the-art ‘Femtosecond’ laser system. This infrared laser, with its ultra-precision, brings the potential to revolutionise eye surgery in the East of England, improving care and ensuring more patients can benefit.

    The femtosecond laser project was led by Mr Madhavan Rajan, Consultant Ophthalmologist in 2016 and he performed the first femto procedure in Cambridgeshire, and since have completed several hundred procedures. Femtolasers help improve safety and accuracy when treating visually compromised patients with cataract and corneal disorders, thanks to Addenbrooke’s Charitable Trust and the Cambridge Eye Trust for their generosity to bring this innovative technology to patients in Cambridge and the East of England region.

    Peer reviewed scientific publications - recent

    Pujari R, Artemis Matsou, Jane Kean, Jufen Zhang, Rajan MS. A Randomized Controlled Trial Comparing Microthin Descemet Stripping Automated
Endothelial Keratoplasty (MT-DSAEK) with Descemet Membrane Endothelial Keratoplasty: 2 year report - Accepted in Cornea 2022.     

    Pujari R, Deshmukh R, Sheth C, Rajan MS. Maternal finger-prick allogenic blood for persistent corneal epithelial defects. BMJ Case Rep. 2021 Apr 9;14(4):e241138. doi: 10.1136/bcr-2020-241138. PMID: 33837031; PMCID: PMC8042995.

    Patra, H. K., Azharuddin, M., Islam, M. M., Papapavlou, G., Deb, S., Osterrieth, J., Zhu, G. H., Romu, T., Dhara, A. K., Jafari, M. J., Ghaderi, A., Hinkula, J., Rajan, M. S., Slater, N. K. H., Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants. Adv. Funct. Mater. 2019, 29, 1903760. https://doi.org/10.1002/adfm.201903760

    Matsou A, Pujari R, Sarwar H, Rana M, Myerscough J, Thomson SM Nandakumar G, Zhang J, Rajan MS. Microthin Descemet Stripping Automated Endothelial Keratoplasty Versus Descemet Membrane Endothelial Keratoplasty: A Randomized Clinical Trial. Cornea. 2020 Nov 3. doi: 10.1097/ICO.0000000000002601. Epub ahead of print. PMID: 33156076.

     Rolev K, Coussons P, King L, Rajan M. Experimental models of corneal endothelial cell therapy and translational challenges to clinical practice. Exp Eye Res. 2019 Nov;188:107794. doi: 10.1016/j.exer.2019.107794. 2019 PMID: 31518569

    Rolev K, OʼDonovan DG, Coussons P, King L, Rajan MS. Feasibility Study of Human Corneal Endothelial Cell Transplantation Using an In Vitro Human Corneal Model. Cornea. 2018 Jun;37(6):778-784. doi: 10.1097/ICO. 0000000000001555. PMID: 29521691.

    Past scientific reports

    1: Bowes OMB, Shah P, Rana M, Farrell S, Rajan MS. Quality indicators in a

    community optometrist led cataract shared care scheme. Ophthalmic Physiol Opt.

    2018 Feb 5. doi: 10.1111/opo.12444. [Epub ahead of print] PubMed PMID: 29405327.

    2: Weber IP, Rana M, Thomas PBM, Dimov IB, Franze K, Rajan MS. Effect of vital

    dyes on human corneal endothelium and elasticity of Descemet's membrane. PLoS

    One. 2017 Sep 13;12(9):e0184375. doi: 10.1371/journal.pone.0184375. eCollection

    2017. PubMed PMID: 28902856; PubMed Central PMCID: PMC5597301.

    3: Rolev K, O'Donovan DG, Georgiou C, Rajan MS, Chittka A. Identification of Prdm

    genes in human corneal endothelium. Exp Eye Res. 2017 Jun;159:114-122. doi:

    10.1016/j.exer.2017.02.009. Epub 2017 Feb 20. PubMed PMID: 28228349; PubMed

    Central PMCID: PMC5451076.

    4: Bassily R, Lencova A, Rajan MS. Bilateral rupture of the posterior capsule and

    intraocular lens dislocation from excessive eye rubbing. J Cataract Refract Surg.

    2016 Feb;42(2):329-31. doi: 10.1016/j.jcrs.2016.01.018. PubMed PMID: 27026458.

    5: Roberts HW, Mukherjee A, Aichner H, Rajan MS. Visual Outcomes and Graft

    Thickness in Microthin DSAEK--One-Year Results. Cornea. 2015 Nov;34(11):1345-50. 

    doi: 10.1097/ICO.0000000000000596. PubMed PMID: 26312621.

    6: Voyatzis G, Roberts HW, Keenan J, Rajan MS. Cambridgeshire cataract shared

    care model: community optometrist-delivered postoperative discharge scheme. Br J 

    Ophthalmol. 2014 Jun;98(6):760-4. doi: 10.1136/bjophthalmol-2013-304636. Epub

    2014 Feb 10. PubMed PMID: 24515987.

    7: Rajan MS. Surgical strategies to improve visual outcomes in corneal

    transplantation. Eye (Lond). 2014 Feb;28(2):196-201. doi: 10.1038/eye.2013.279.

    Epub 2014 Jan 3. Review. PubMed PMID: 24384964; PubMed Central PMCID: PMC3930281.

    8: Thomas PB, Mukherjee AN, O'Donovan D, Rajan MS. Preconditioned donor corneal

    thickness for microthin endothelial keratoplasty. Cornea. 2013 Jul;32(7):e173-8. 

    doi: 10.1097/ICO.0b013e3182912fd2. PubMed PMID: 23665648.

    9: Hyatt AJ, Rajan MS, Burling K, Ellington MJ, Tassoni A, Martin KR. Release of 

    vancomycin and gentamicin from a contact lens versus a fibrin coating applied to 

    a contact lens. Invest Ophthalmol Vis Sci. 2012 Apr 18;53(4):1946-52. doi:

    10.1167/iovs.11-8607. PubMed PMID: 22408014.

    10: Hayes S, Boote C, Kamma-Lorger CS, Rajan MS, Harris J, Dooley E, Hawksworth

    N, Hiller J, Terill NJ, Hafezi F, Brahma AK, Quantock AJ, Meek KM. Riboflavin/UVA

    collagen cross-linking-induced changes in normal and keratoconus corneal stroma. 

    PLoS One. 2011;6(8):e22405. doi: 10.1371/journal.pone.0022405. Epub 2011 Aug 5.

    PubMed PMID: 21850225; PubMed Central PMCID: PMC3151245.

    11: Daniel CS, Rajan MS, Saw VP, Claerhout I, Kestelyn P, Dart JK. Contact

    lens-related Fusarium keratitis in London and Ghent. Eye (Lond). 2009

    Feb;23(2):484-5. doi: 10.1038/eye.2008.188. Epub 2008 Jul 4. PubMed PMID:


    12: Shortt AJ, Secker GA, Rajan MS, Meligonis G, Dart JK, Tuft SJ, Daniels JT. Ex

    vivo expansion and transplantation of limbal epithelial stem cells.

    Ophthalmology. 2008 Nov;115(11):1989-97. doi: 10.1016/j.ophtha.2008.04.039. Epub 

    2008 Jun 13. PubMed PMID: 18554721.

    13: Rajan MS, Bunce C, Tuft S. Interocular axial length difference and

    age-related cataract. J Cataract Refract Surg. 2008 Jan;34(1):76-9. doi:

    10.1016/j.jcrs.2007.08.023. PubMed PMID: 18165085.

    14: Rajan MS, O'Brart D, Jaycock P, Marshall J. Effects of ablation diameter on

    long-term refractive stability and corneal transparency after photorefractive

    keratectomy. Ophthalmology. 2006 Oct;113(10):1798-806. PubMed PMID: 17011958.

    15: Rajan MS, O'Brart DP, Patmore A, Marshall J. Cellular effects of mitomycin-C 

    on human corneas after photorefractive keratectomy. J Cataract Refract Surg. 2006

    Oct;32(10):1741-7. PubMed PMID: 17010877.

    16: Rajan MS, O'Brart DP, Patel P, Falcon MG, Marshall J. Topography-guided

    customized laser-assisted subepithelial keratectomy for the treatment of

    postkeratoplasty astigmatism. J Cataract Refract Surg. 2006 Jun;32(6):949-57.

    PubMed PMID: 16814052.

    17: Rajan MS, Pantelidis P, Tong CY, French GL, Graham EM, Stanford MR. Diagnosis

    of Treponema pallidum in vitreous samples using real time polymerase chain

    reaction. Br J Ophthalmol. 2006 May;90(5):647-8. PubMed PMID: 16622098; PubMed

    Central PMCID: PMC1857041.

    18: Rajan MS, Watters W, Patmore A, Marshall J. In vitro human corneal model to

    investigate stromal epithelial interactions following refractive surgery. J

    Cataract Refract Surg. 2005 Sep;31(9):1789-801. PubMed PMID: 16246786.

    19: Jaycock PD, O'Brart DP, Rajan MS, Marshall J. 5-year follow-up of LASIK for

    hyperopia. Ophthalmology. 2005 Feb;112(2):191-9. PubMed PMID: 15691550.

    20: Rajan MS, Shafiei S, Mohrenfels CV, Patmore A, Lohmann C, Marshall J,

    Hamberg-Nystrom H. Effect of exogenous keratinocyte growth factor on corneal

    epithelial migration after photorefractive keratectomy. J Cataract Refract Surg. 

    2004 Oct;30(10):2200-6. PubMed PMID: 15474836.

    21: Rajan MS, Jaycock P, O'Brart D, Nystrom HH, Marshall J. A long-term study of 

    photorefractive keratectomy; 12-year follow-up. Ophthalmology. 2004

    Oct;111(10):1813-24. PubMed PMID: 15465541.

    22: Sobha S, Rajan MS, Jackson H. Choroidal neovascularization following

    hyperopic LASIK surgery. Clin Exp Ophthalmol. 2004 Aug;32(4):443-5. PubMed PMID: 


    23: Rajan MS, Syam P, Liu C. Systemic side effects of topical latanoprost. Eye

    (Lond). 2003 Apr;17(3):442-4. PubMed PMID: 12724721.

    24: Kielhorn I, Rajan MS, Tesha PM, Subryan VR, Bell JA. Clinical assessment of

    the Zeiss IOLMaster. J Cataract Refract Surg. 2003 Mar;29(3):518-22. PubMed PMID:


    25: Rajan MS, Bremner FD, Riordan-Eva P. Pupil perimetry in the diagnosis of

    functional visual field loss. J R Soc Med. 2002 Oct;95(10):498-500. PubMed PMID: 

    12356970; PubMed Central PMCID: PMC1279175.

    26: Rajan MS, Keilhorn I, Bell JA. Partial coherence laser interferometry vs

    conventional ultrasound biometry in intraocular lens power calculations. Eye

    (Lond). 2002 Sep;16(5):552-6. PubMed PMID: 12194067.

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