“Although limbal stem cell deficiency (LSCD) is a rare condition, this really is an umbrella term that we use to describe a heterogeneous group of diseases,” said Christine Shieh, MD, during Pediatric Ophthalmology Subspecialty Day. The manifestations of LSCD can vary widely among pediatric patients and have different considerations and clinical outcomes. Because the symptoms are not specific, physicians should rely on clinical exams to diagnose early disease, said Dr. Shieh during the on demand session “Anterior Segment Innovators and Influencers.”
Genetic disease. LSCD can be categorized as genetic or acquired disease. Genetic causes can be isolated to the eye or can be syndromic with nonocular findings, as with aniridia, for example. It is important to also note that aniridia is not limited to autosomal dominant inheritance but can be sporadic or autosomal recessive. “The signs of limbal stem cell deficiency in these genetic conditions tend to be minimal when these pediatric patients are young and worsen as the time passes,” Dr. Shieh said.
Acquired disease. Acquired LSCD most commonly results from chemical or thermal injury. As with most ocular trauma, these cases occur more often in boys than girls. Contact lens use—though rarely associated with severe LSCD in young patients—is one of the most common causes of medically reversible LSCD.
LSCD can also result from autoimmune inflammatory conditions, she said. In such cases, “It generally takes conditions that create severe inflammation such as Stevens-Johnson syndrome or graft-vs.-host disease that can affect the whole body.” It may sometimes occur in severe cases of diseases limited to the eye, such as ocular rosacea or vernal keratoconjunctivitis, as well.
Topical medications and surgical procedures may lead to iatrogenic deficiency. “As physicians, we can’t ignore the role we play in causing limbal stem cell deficiency, either from the surgeries we perform or from our prescription eyedrops,” Dr. Shieh added.
Medical management. In 2019, the Limbal Stem Cell Working Group established a staging system for LSCD, reporting that stage I and IIA disease could be managed medically, while more severe stages required surgical interventions.
Medical management of LSCD involves either stopping traumatic or toxic insults to the limbus or initiating medical therapy aimed at optimizing the ocular surface environment. Treatments generally focus on improving the tear film (e.g., preservative-free tears or punctal plugs), controlling inflammation (e.g., cyclosporine [Restasis], lifitegrast [Xiidra], or tacrolimus ointment [off-label in the United States]), or optimizing epithelial homeostasis (e.g., off-label vitamin A or blood-derived eyedrops).
Dr. Shieh also noted that several adjunct treatment options are available. Patients with partial LSCD may benefit from sectoral superficial keratectomy, alone or with amniotic membrane. It is important, however, to remember that amniotic membrane is not a sustainable long-term option for severe LSCD.
Limbal stem cell transplants. Transplants can be classified by the source of donor tissues and are generally autologous—which tend to lead to better outcomes—or allogeneic and either grafted in vivo or cultivated ex vivo. However, since the early signs of LSCD can be subtle, Dr. Shieh warns against harvesting limbal stem cells from the seemingly healthy donor eye of a contact lens wearer.
Other procedures. One autologous surgical approach for treatment of LSCD is simple limbal epithelial transplantation (SLET), developed by Virender Sangwan, MBBS, and colleagues. In this method, 2-by-2-mm limbal grafts are harvested from the healthy fellow eye and transplanted onto the stem cell–deficient eye via a fresh amniotic membrane and fibrin glue.
Another technique is living related conjunctival limbal allograft transplantation (also called the Cincinnati procedure) developed by Edward Holland, MD. His team has shown that allogeneic ocular surface stem cell transplantation can be a successful option for pediatric LSCD and that systemic immunosuppression is generally well tolerated. —Kanaga Rajan, PhD
Watch Dr. Shieh’s full presentation. If you are registered for AAO 2020 Virtual, you have access to the on demand presentations. Log in to the virtual meeting platform: Next, from Lobby screen, hover your pointer over “On Demand” in the top navigation, and select “On Demand Presentations” from the drop-down menu and then search for event code “Ped09.06”.
Financial disclosures. Dr. Shieh: None.
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