What is the best method to manage limbal stem cell deficiency?
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OSST first choice
Limbal stem cell deficiency with or without conjunctival deficiency can lead to sequelae that result in severe visual loss. While an ocular surface stem cell transplantation, or OSST, and keratoprosthesis are both viable options to rehabilitate vision, OSST should be seen as the first choice for most patients.
An OSST provides healthy limbal stem cells and conjunctiva to address the limbal stem cell deficiency. For unilateral disease, OSST autograft procedures (eg, conjunctival limbal autograft) have demonstrated excellent intermediate-term and long-term ocular surface stability (83% to 88% success rates, respectively) and significant visual improvement (71% to 88% with a two-line improvement). Bilateral disease requires an OSST allograft procedure with appropriate triple-agent systemic immunosuppression (includes tapering corticosteroid); studies with these systemic immunosuppression regimens have shown 73% to 83% achieve long-term surface stability and 62% to 92% with two-line visual improvement. With appropriate monitoring by a cornea specialist and organ transplant physician, the risk for irreversible toxicity at recommended dosages of systemic immunosuppression in this population is minimal.
There are more potential vision-threatening complications associated with keratoprosthesis than OSST. Because the underlying limbal stem cell deficiency is not addressed, eyes with a keratoprosthesis may still have persistent epithelial defects, leading to an increased risk for infectious keratitis and corneal stromal necrosis. Additional potential blinding complications with keratoprosthesis include glaucoma, endophthalmitis and retinal detachment. There may also be high rates of major surgery for postoperative complications after keratoprosthesis implantation. With failure of an OSST, ocular surface failure causes return to baseline vision; however, the more serious complications with keratoprosthesis, although rare, may result in loss of vision or the eye.
Despite an often faster visual recovery with keratoprosthesis, our group found progressive loss of this initial visual improvement (74% with two-line improvement decreased to 43.5%) over a mean 4.5 years’ follow-up in patients with aniridia undergoing keratoprosthesis placement. Glaucoma was a significant cause of vision loss, which is difficult to monitor with a keratoprosthesis, although OSST still allows for normal monitoring of IOP. Even if a keratoprosthesis is eventually required for better vision, a prior primary OSST may help decrease keratolysis risks and improve retention in this difficult population.
Cornea specialists and ophthalmologists should understand that systemic immunosuppression is safe with proper monitoring. The complications of OSST may lead to loss of the ocular surface but not loss of the eye, while certain keratoprosthesis complications may lead to irreversible blindness. The majority of published keratoprosthesis data are in patients without severe ocular surface disease; however, there are higher rates of complications in this population.
References:
Aravena C, et al. Cornea. 2016;doi:10.1097/ICO.0000000000000933.
Burcu A, et al. Cutan Ocul Toxicol. 2014;doi:10.3109/15569527.2013.796477.
Chan CC, et al. Cornea. 2016;doi:10.1097/ICO.0000000000000911.
Eslani M, et al. Ocul Surf. 2019;doi:10.1016/j.jtos.2019.09.003.
Holland EJ, et al. Cornea. 2012;doi:10.1097/ICO.0b013e31823f8b0c.
Hou JH, et al. Cornea. 2012;doi:10.1097/ICO.0b013e31823e2ac6.
Javadi MA, et al. Ophthalmology. 2011;doi:10.1016/j.ophtha.2010.11.012.
Liang L, et al. Arch Ophthalmol. 2009;doi:10.1001/archophthalmol.2009.263.
Miri A, et al. Ophthalmology. 2010;doi:10.1016/j.ophtha.2009.10.028.
Movahedan A, et al. Am J Ophthalmol. 2017;doi:10.1016/j.ajo.2017.10.002.
Santos MS, et al. Am J. Ophthalmol. 2005;doi:10.1016/j.ajo.2005.03.022.
Shah KJ, et al. Cornea. 2018;doi:10.1097/ICO.0000000000001412.
Wylegala E, et al. Eur J Ophthalmol. 2008;doi:10.1177/112067210801800605.
Yao YF, et al. Ophthalmology. 2002;doi:10.1016/s0161-6420(02)01258-7.
Albert Y. Cheung, MD, is a board-certified ophthalmologist with Virginia Eye Consultants. Disclosure: Cheung reports no relevant financial disclosures.
Boston keratoprosthesis increasingly accepted
The Boston type 1 keratoprosthesis was first approved for use by the FDA in 1992, developed for patients who are poor candidates for traditional full-thickness corneal transplantation because of a high risk for graft failure or rejection. The indications for keratoprosthesis implantation include recurrent corneal graft failure, herpetic disease and limbal stem cell deficiency secondary to chemical burns and aniridia. Although patients with autoimmune conditions such as ocular cicatricial pemphigoid and Stevens-Johnson syndrome can also benefit from keratoprosthesis, the prognosis is guarded.
The keratoprosthesis is made of PMMA and comes in two designs. Type 1 is shaped like a collar button and is inserted into a corneal graft. This is most commonly used and recommended in eyes with relatively intact blink and tear secretion. Type 2 has an additional nub to be exposed through the upper lid skin in end-stage dry eyes such as Stevens-Johnson syndrome.
Initial keratoprosthesis implantation was associated with poor outcomes related to implant extrusion, corneal necrosis and endophthalmitis. As modifications in the implant design and postoperative management have evolved, the retention rates of the Boston type 1 keratoprosthesis have dramatically improved, making the procedure an increasingly accepted alternative to standard keratoplasty in eyes with an unacceptably high risk for corneal graft failure. With a reduction in acute complications, the long-term visual outcomes after keratoprosthesis surgery have also improved but are still limited by chronic diseases such as glaucoma. A successful outcome requires considerable patient compliance and more frequent follow-up. However, in cases in which further keratoplasty is unlikely to succeed, keratoprosthesis can significantly improve vision and quality of life.
Patients with limbal stem cell deficiency are at increased risk for graft failure in autoimmune conditions such as Stevens-Johnson syndrome. Keratolimbal allografts in conjunction with corneal transplantation can significantly improve outcomes but require long-term systemic immunosuppression with potentially serious adverse events, which can limit consideration in many patients. Keratoprosthesis can provide an alternative to standard keratoplasty and keratolimbal allografts in the setting of stem cell deficiency, eliminating the need for long-term systemic immunosuppression with prednisone and other steroid-sparing agents. Keratoprosthesis also has the advantage of providing faster recovery of vision given the need for staging surgery with keratolimbal allografts and visual recovery being dependent on astigmatism management with standard keratoplasty. In addition, risk for graft rejection is eliminated. Keratoprosthesis does, however, require closer follow-up to manage risk for infection, corneal melting and glaucoma. Long-term prognosis after keratoprosthesis surgery is good with noninflammatory conditions but is guarded with autoimmune conditions.
Shahzad I. Mian, MD, is a professor of ophthalmology at Kellogg Eye Center in Ann Arbor, Michigan. Disclosure: Mian reports no relevant financial disclosures.
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