Introduction
Blindness continues to be one of the major public health problems in developing countries. Cataract and corneal diseases are major causes of blindness in countries with less-developed economies.
Out of all the causes for corneal blindness, chemical injuries carry a poor prognosis as they may result in damage of the limbal stem cells and cause limbal stem cell deficiency (LSCD). Chemical injuries to the eye can produce extensive damage to the ocular surface leading to visual impairment and disfigurement therefore there is need of LSCT to prevent this potentially blinding condition. Depending on the source of the donor tissue, LSCT can either be autologous (from the unaffected fellow eye of the same person) or allogeneic (from another person).
Various treatment modalities have been described over the past few decades for the treatment of limbal stem cell deficiency including Conjunctival limbal autograft (CLAU), keratolimbal allograft (KLAL), Cultivated limbal epithelial transplantation(CLET), Simple limbal epithelial transplantation (SLET).
Simple Limbal Epithelial Transplantation (SLET) is a surgical technique first described by Dr. Sangwan1 in 2012 for the treatment of limbal stem cell deficiency (LSCD). SLET is a reproducible, single stage technique without the need of a special laboratory setup.
Materials and Methods
It was a single centre prospective interventional case series study conducted over a span of one year from December 2018 to November 2019. The proposed study was carried out at the Regional Institute of Ophthalmology (M.D. Eye Hospital, Dr. Katju Road, Nakhas Kona, Prayagraj) after taking permission from ethical committee of M.L.N. Medical College, Prayagraj. After examining 15 patients of Chronic LSCD randomly, 5 patients were undertaken for SLET surgery. The study included the chronic cases of chemical injury (Acid and alkali injury) and excluded the cases of LSCD secondary to causes other than chemical injury or cases with dry eye.
Pre operatively all patients underwent general and ophthalmic evaluation which includes history (demographic details, etiology of LSCD, injury to presentation duration, prior surgery performed, presentation to SLET duration), general Examination, best corrected visual acuity (BCVA), ocular examination including slit lamp examination (presence or absence of eye lid abnormalities, symblepharon and persistent epithelial defects were noted), anterior segment OCT, B-scan ultrasonography, blood investigation (haemoglobin, total leucocyte count, differential leucocyte count, blood sugar, HIV, HBsAg, HCV antigen, coagulation profile).
Anterior segment OCT
Scan images were taken by high-definition cirrus optical coherence tomography (Cirrus HD OCT software version 6.5.0.772; Carl Zeiss Meditec).
Pre operative anterior segment OCT is essential before planning a simple limbal epithelial transplant in cases of chemical injury, in order to-
Assess the level of corneal scarring.
Rule out pre existing corneal perforation.
Assess corneal thickness in order to observe vulnerable areas to avoid perforation intra operatively.
Patients were followed for minimum of 3-6 months period
Observation and Results
During this study, we have examined 15 patients of chronic limbal stem cell deficiency out of which, after thorough slit lamp examination and ruling out dry ocular surfaces, we have performed simple limbal epithelial transplantation.
Table 1
Characterstics of patients undergoing simple limbal epithelial transplantation for unilateral limbal stem cell deficiency
Discussion
In this study, the simple limbal epithelial transplantation technique was used to restore corneal epithelium in 5 patients with unilateral stem cell deficiency. Out of all the causes of limbal stem cell deficiency, we found that chemical injury due to alkali contributes maximum number.
Prognostic categorization of patients
Ideal patient for this procedure(SLET) are patients with unilateral stem cell deficiency with clinically non inflamed wet ocular surface. schirmer’s test and fluorescein staining was done pre operatively to assess the degree of wettability. Prognostic categorization was done based on presenting features in the affected eye. Schirmer’s test was done it was found that out of 5 patient studied, 3 patient shows normal >15mm of wetting of schirmer’s strip, 1 patient shows mild and 1 patient shows moderate grade of schirmer’s test.
Patient 1 had minimal conjunctival inflammation with absent dryness no prior history of AMG, or history of multiple surgery previously. No eye lid abnormality was seen, organised anterior segment and normal digital IOP. Patient 2 has presence of symblepharon superiorly with no history of previous surgery. Patient 3 presented to us 10 months back in acute phase of lime injury and was managed conservatively. After two months patient developed LSCD, it was complicated by presence of symblepharon superiorly and inferiorly. Patient 4 had history of multiple surgeries previously, there was severe conjunctival inflammation, a patch of keratinization and corneal thickness of 300 micron was present and schirmer’s in this case was of moderate grade. Patient 5 too had history of previous surgery elsewhere, presence of symblepharon superiorly, keratinization with adequate stromal and pannus thickness, history of MMG was assessed clinically and intraoperatively it was found amniotic membrane graft was done. As per the grading of limbal stem cell deficiency patients given by Shanbag et al,2 Patient 1,2 3 were graded as fair and patient 4,5 as poor.
Ocular surface stabilisation
In our study, stable corneal surface was achieved in 4 (80%) cases out of 5 by 2 weeks. Patient 4 got epithelial defect at post operative day 21 which healed by 4 weeks. In patient 5 we found epithelial defect in inferior cornea at day 14, so we placed the bandage contact lens thereafter again, patient had stable ocular surface by 4 weeks. Sangwan et al1 followed patients for 1 year and found a completely avascular and stable surface by 6 weeks in all six patients he studied. SLET with sandwich technique was done by Amescua et al3 in 4 patients with unilateral partial (2 eyes) and total (2 eyes) limbal stem cell deficiency secondary to ocular burn. Regular corneal epithelium and a quiet ocular surface was obtained in all 4 patient by 4 weeks. A multicentric study by Vazirani et al4 was done in 68 eyes of 68 patients who underwent SLET across eight centre in three countries. 57 patients (80%) were having completely, avascular corneal surface.
Complications
No studies have reported serious adverse outcomes of the donor eye. Localised, non progressive focal LSCD of donor site was reported in two cases which do not affect visual acuity in study by Vazirani et al.4 Pyogenic granuloma was also reported in two donor eyes at the site of limbal tissue excision in a study by Basu et al.5 The most common complication of the recipient eye after SLET was focal recurrence of LSCD which was reported in 18% to 31% eyes.
We found that none of the fellow eyes demonstrated any donor site LSCD or other complications. Typically, the donor site epithelial defect had completely healed by 1 week. The most common observation in the donor eye was subconjunctival haemorrhage, which resolved by 1 month in all cases.
In our study, in the recipient eye focal recurrence was seen in second patient (20%) after 2 months, symblepharon in third patient (20%), self limiting haemorrhage under amniotic membrane in 4 patients (80%), loss of transplants in one patient (20%), keratitis in fourth patient (20%).
In our series of patients, early complication (<3 days) included haemorrhage under amniotic membrane which usually resolved without any consequences. Intermediate complication (4-15days) included epithelial defect, and microbial keratitis. Delayed complication (15 days- 3 months) which were seen in our patients includes neovascularization, focal recurrence and symblepharon.
Focal recurrence was noticed in the area of maximum severity of preoperative symblepharon. Hence, one of the causes for such recurrence could be the extensive damage of the conjunctiva during initial injury and a focal loss of the conjunctival stem cell. Since, the focal recurrence in our patient was neither progressive nor encroaching the pupillary area, we do not opted for resurgery.
Neovascularisation was seen in patient 1 after SLET surgery at day 45 which was managed by giving oral steroids. This is contrary to previous studies because most of the immunological rejection is seen following allogenic simple limbal epithelial transplantation. But since the neovascularisation regressed following the administration of oral steroids, we believe that there may be a component of immunity involving auto-SLET as well.
Patient 4 (20%) presented with microbial keratitis at post operative day 7 with loss of amniotic membrane with loss of limbal grafts. None of the previous studies mentioned clearly about the microbial keratitis following SLET. Nevertheless, since total corneoscleral surface is bared, and post operatively steroid drops were instilled, it could be well appreciated that loss of amniotic membrane will predispose to infection.
Risk factors
We found presence of symblepharon, post operative loss of limbal grafts history of previous surgery, duration of injury to SLET duration were the possible risk factors for the poor outcome of the surgery. To avoid perforation, thin corneas should be identified using an OCT before the surgery. However, OCT examination is not full proof for avoiding perforation intraoperatively and one should be ready with cyanoacrylate glue &/or tenon patch graft for management of perforation.
Visual acuity
Rates of improvement of visual acuity in this study are comparable with those reported in earlier studies. In our study, improvement of visual acuity was seen in 3(60%) patient out of 5 cases operated. Pre-SLET visual acuity were HM (four eyes), 6/18 (one eye). Post SLET visual acuity were 6/12 (one eye), 6/60 (one eye), CF (one eye), HM (two eyes) at final follow-up. A longer injury to SLET duration have poor impact on prognosis of results. Two patients achieved stable corneal surface but with only one line improvement of vision, the probable explanation would be amblyopia. In a study by Vikas Mittal et al,6 he recommends timely SLET in paediatric patients of LSCD in order to avoid amblyopia as well as timely management of amblyopia.Visual acuity improved from worse than 6/60 in all recipient eyes before surgery to 6/12 or better in all four eye(100%) in a study by Sangwan et al.1
Limitations
One of the lacunae in our study was the smaller sample size, but review of literature also shows that the smaller size in previous studies as chemical injury patients are infrequent. Out of chemical injury patients only few percent of patients are ideal candidates for SLET. We have encountered 15 patients of chronic LSCD, out of those we performed surgery in only 5 patients because patients selection is important criteria for success of SLET surgery.
Procurement of amniotic membrane and use of BAXTER glue were the cost limiting factors in this study as we have conducted study in a regional institute, most of the patients were from poor socio economic background. We need more patients and longer follow-ups to assess the exact surgical outcome. However, the initial results are very encouraging. We believe especially in developing countries, where the patients cannot afford expensive surgeries like CLET, it should be treatment of choice for unilateral LSCD.
The uniqueness of this study is its authenticity, with a minimum follow-up of at least 6 months involving a regional institute of mostly rural population. Furthermore, a single surgeon, eliminating chances of interobserver variations, did the surgery and all the follow-ups.
Conclusion
To conclude, considering the satisfactory initial results we obtained in four of our five patients, it seems that the SLET technique may be a good alternative in treating unilateral total limbal stem cell deficiency. Some modifications must be devised to allow its usage in dry eye patients, as majority of the chronic LSCD patients on which we couln’t operate were of dry eye.
