Penetrating corneal grafts for infantile corneal opacity: a waste of time?

Abstract

Corneal transplantation surgery in an infant eye presents with a wide variety of problems ranging from the preoperative assessment to the postoperative follow-up. The presence of amblyopia and associated ocular pathologies significantly limits the visual outcomes. Thus, few years back corneal surgeons used to avoid penetrating grafts in an infant eye. However, vigilant case selection, advances in surgical techniques, and meticulous postoperative care has lead to an improvement in the overall outcomes. Thus, penetrating corneal grafts in an infant eye is no longer considered a waste of time rather it has become an invaluable tool for visual rehabilitation of infants with corneal opacity.

Keywords:

• amblyopia
• childhood blindness
• graft failure
• infantile corneal opacity
• penetrating keratoplasty

Corneal blindness remains a leading cause of childhood visual impairment worldwide. The problem is much worse in the developing countries where infection and malnutrition are still a major concern [1]. A survey by Kurilec and Zaidman [2] found that in US approximately one infant corneal transplant is performed for every 24,000 live births and most of the congenital corneal opacities (CCO) interfering with vision are related to Peters Anomaly. Infantile corneal opacities can be categorized into three main groups; congenital, acquired non-traumatic, and acquired traumatic corneal opacities [3]. Common causes of CCO include Sclerocornea, Peters anomaly, and congenital glaucoma. Rare causes include anterior staphyloma/keratectasia, corneal dystrophies, mucopolysaccharidoses, mucolipidoses, and congenital corneal tumors [3,4].

Management of corneal opacities in an adult patient is more or less straightforward. Treating physician gets enough time to plan for the surgery or even try other modalities before proceeding for penetrating keratoplasty (PKP). Infantile corneal opacity does not provide the same liberty in terms of time and surgical choices. Amblyopia and its prevention play an important role in both decision-making as well as postoperative care [5]. Few years back most corneal surgeons would avoid PKP in an infant eye. However advances in tools for preoperative evaluation, surgical technique, and postoperative care have lead to a significant improvement in the surgical outcomes as a result of which, PKP in infants is being performed with increasing frequency and success [5]. It is often the treatment of choice for many corneal surgeons in a carefully selected group of infants with corneal opacities. Nevertheless, prognosis for PKP in an infant is guarded and is definitely not as good as for adults. Graft survival and visual results often remain disappointing due to high rate of graft failure (most commonly due to rejection and infection) and high rate of vision loss from amblyopia despite maintaining a clear graft [5].

The poor outcomes of transplants in infants are due to unique preoperative, intraoperative, and postoperative factors [6]. Preoperatively, the assessment of visual function and visual potential is difficult in an infant. Intraoperatively, the smaller and more crowded anterior segment, reduced rigidity and increased elasticity of the cornea and sclera, makes the surgery difficult. Reduced scleral rigidity makes suturing difficult, and a high positive vitreous pressure makes the surgery extremely challenging with an increased chance of complications, such as vitreous loss and aphakia [6]. Postoperatively, an aggressive immune system leads to an increased risk of graft rejection. A rapid wound healing process can result in early loosening of the sutures with its associated consequences. All of this is further complicated by the inability of the child to communicate thus making early diagnosis and treatment extremely difficult. Finally, even when anatomic success is achieved in terms of graft survival, the management of amblyopia is often difficult and ultimately limits the functional outcome in terms of visual recovery. The frequent presence of coexisting ocular pathology further adds to a poor visual outcome in such cases.

A review of the published data reveals variable success with PKP in pediatric age group. Data derived from these studies are often inadequate to derive a firm conclusion due to few cases, paucity of visual acuity data, and lack of long-term follow-up. Overall graft survival ranges from 27 to 100% and chances of getting a BCVA of 20/60–20/400 ranges from 6 to 48%, with mean age at surgery ranging from 5 months to 12 years [7]. Very few studies have specifically analyzed the outcome of PKP in Infants. One of the earliest report by Hertle and Orlin [8] reported excellent graft survival and visual outcomes at 6 years following PKP in two infants within the first 3 weeks of life. The authors attributed the excellent visual outcome to the prompt amblyopia treatment and optical therapy after surgery [8]. Another study by Huang et al. [9] reported a fair overall prognosis of 54% graft survival at 1 year in 106 PKPs performed in pediatric patients. Out of 106 patients, 25 patients were younger than 6 months, and 13 patients were between 6 months and 5 years old. The interesting part in this study was that the graft survival at 1 year was similar among different age groups (younger than 6 months: 48%, 6 months to 5 years: 67%, older than 5 years: 51%). Pre-transplant and/or post-transplant glaucoma was associated with worse 1-year graft survival (glaucoma 32% vs. no glaucoma 70%). However, the visual outcomes were poor and CCO group had the worse vision compared with the acquired opacities group. Rao et al. [10] reported a graft survival of 22% at 2 years in 40 corneal transplants in cases with Peters anomaly. Thirteen of these cases were less than 6 months old. Poor graft survival correlated with young age since 85% of the grafts failed in infants who were 6 months old. Zaidman et al. [11] reported graft survival of 90% in Peters Type I with mean age of 5 months at the time of surgery and BCVA of <20/60 in 29% and 20/60–20/400 in 25% of cases. Kim et al. [12] reported outcomes of PKP in 20 eyes of 18 patients (eight Peters anomaly, 10 sclerocornea). The authors reported better surgical outcome in patients with Peters anomaly, compared with sclerocornea. The overall graft survival rate was 50%. Large trephine size and corneal diameter were associated with better outcome in terms of a lesser chance of graft rejection. There was no significant difference in the graft survival rate among the age groups but graft rejection occurred most frequently in patients aged between 12 and 48 months [12]. Yang et al. analyzed the corneal graft survival after PKP in 144 eyes with Peters anomaly. The median age at first keratoplasty was 4.4 months. The overall probability of maintaining a clear first graft was 56% at 6 months, 49% at 12 months, 44% at 3 years, and 35% at 10 years. Eyes with severe disease, large donor corneas, coexisting central nervous system abnormalities, and anterior synechiae had significantly poorer outcomes [12].

Overall, it can be concluded that the outcomes of PKP in infants is fair to good in terms of graft survival. However, the results are not encouraging in terms of functional outcomes. Many authors have tried alternative treatment modalities but these are possible only in selected cases [13,14]. Does that mean a PKP in an infant eye is a waste of time? The answer lies in the fact that there are certain situations where this is the only treatment option to offer. In infants with unilateral disease, the risk of irreversible dense amblyopia outweighs the risk associated with performing a PKP. Similarly in bilateral cases, the procedure can be delayed for a few months but not for years. Hence, bilateral cornea transplantation in a staged fashion is recommended.

Therefore, instead of assuming PKP in an infant as wastage of time, every effort must be made to improve the outcomes of the surgery. Timing of surgery, intraoperative precautions, and a well-planned anti-amblyopia approach can improve the outcomes significantly. Optimal timing for surgical intervention remains controversial. In cases of unilateral opacities, PKP must be done at the earliest while bilateral opacities should ideally be operated between the second and third months of life. The second transplantation should then be performed within 2–4 week to avoid amblyopia. Donor tissue must be of high quality with an endothelial count 3000 cells per mm² or more. Use of Flieringa ring may reduce the chances of vitreous loss and makes suturing easy. Postoperative care is extremely important in these cases. The child is started on topical antibiotics and corticosteroid eye drops which are gradually tapered over several months. Antiglaucoma medications are added in case of vitreous loss or preexisting glaucoma. The most common causes of allograft failure are graft rejection, glaucoma, and infection [5]. The common complications encountered are glaucoma, cataract, infectious keratitis, and suture-related problems [5]. Timely removal of sutures, careful monitoring for development of glaucoma, cataract and retinal disorders are important.

It is important for both the treating physician and the parents to realize that PKP is only the first step in visual rehabilitation and effective amblyopia therapy during child’s first years of life establishes the eye’s lifelong visual potential. Virtually all infants have some degree of amblyopia because of either visual deprivation before the surgery, graft astigmatism, anisometropia, or a combination of these. Therefore, aggressive amblyopia treatments should be started as soon as possible.

Alternative treatments options to PKP have been described to avoid a full thickness graft in infants. Optical iridectomy and ipsilateral rotational autokeratoplasty may be used in patients with localized corneal opacity. Lamellar keratoplasty techniques, such as deep anterior lamellar keratoplasty and endothelial keratoplasty have been shown to be promising in pediatric eyes [15–17]. However, these procedures are technically challenging in an infant eye and require very careful case selection.

To conclude, the visual outcomes after PKP in infants are poor despite good anatomical outcomes. Nonetheless, with careful case selection and careful intra- as well as post-operative management some functional vision can be achieved in most cases. It is important to realize that a visual acuity of even ability to count fingers can be a great psychological boost for the child as well as the parents. With modern low vision aid devices, rehabilitation of such patients both socially as well as economically can be achieved. Thus, PKP in an infant eye is extremely useful and at times the only option in few selected cases.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.