In this study, the primary goal of sealing the corneal perforation was achieved in 28 eyes (68.3%) of the 41 eyes after the first operation, and in 34 eyes (82.9%) of 41 eyes on final observation. We used cryopreserved donor corneas for therapeutic keratoplasty (41 eyes, 100%). In Japan, donor organs including corneas are in short supply. Thus, ophthalmologists do not always have access to fresh donor organs when needed on an emergency basis. A previous report suggested that cryopreserved donor corneas have a high risk for recurrence of reperforation and infection.4 According to their study, sometimes a second keratoplasty using fresh donor grafts is needed to recover corneal transparency.4 However, in the report by Hanada et al. with 67% fresh donor corneas used in therapeutic corneal transplantation, the cure rate was 80%, which is not so different from that of our study, and there was also no difference in the rate of complications.13
If in bacterial or fungal keratitis the infected lesion was incompletely removed, reoccurrence of the infectious keratitis was sometimes observed. A previous report showed that it is necessary to remove the focus of infection by oversizing 0.5 mm to 1.0 mm.23 Yokogawa et al.23 reported corneal transplantation for corneal perforation by bacterial and fungal keratitis performed with small grafts, however, a second large graft was eventually required for all cases. Li et al. reported therapeutic corneal transplantation in 116 cases of fungal keratitis and found that graft rejection and secondary glaucoma were more likely to occur in large grafts.11 Other reports described that large grafts are associated with poor postoperative prognosis and complications.24–26 On the other hand, there are reports that a large graft size does not influence the postoperative prognosis.10,27 Considering these study findings, publications regarding the effects of the graft size on anatomical recovery rate and complications were gathered only for cases of infectious keratitis such as bacterial, fungal, and acanthamoeba keratitis, and they were similar to the results in the present study. The group with grafts 8.5 mm or larger was less controlled with appropriate treatment than that with grafts smaller than 8.5 mm. Among the cases using 8.5 mm or larger grafts in the infection group, all 5 eyes with bacterial or fungal keratitis did not achieve the sealing of the corneal perforation. Koçluk et al. reported 25 cases of bacterial and fungal keratitis divided into two groups according to the time until the surgical intervention (> 15 days vs ≤ 15 days). As a result, there were more large grafts (diameter ≥ 9.5 mm) in the group with the longer time until intervention.24 Our findings may demonstrate some important points when sealing corneal perforations in cases of bacterial and fungal keratitis; primarily that infected lesion should be completely removed and secondly that therapeutic keratoplasty should be performed before the focus of infection reaches the vicinity of the limbus.
Among the cases with secondary surgery for infections, both the proportion of optical indications and the cure rate were high. In non-infectious cases, there was a higher incidence of tectonic surgery. After the second transplantation, the cure rate was 100% in infectious cases, of which the visual acuity improved in 71.4%, and there were no cases with decreased visual acuity. This shows that a second optical operation is good option for visual acuity improvement after the infection is under control.
Penetrating keratoplasty is the most common surgical procedure in both infectious and non-infectious diseases with corneal perforations. Recently, some authors reported that LKP and deep anterior lamellar keratoplasty (DALK) for corneal perforation is safer in terms of endothelial rejection.10,19,21,27−33 Other studies have noted that Descemet stripping automated endothelial keratoplasty (DSAEK) is effective for perforation cases.33 Nevertheless, a disadvantage of LKP is the possibility that the infected lesion may not be completely removed and interface opacity may cause blurred vision.21 Shimmura et al. proposed that good visual acuity was achieved by DALK performed on therapeutic transplantation and that it is necessary to select a surgical method with the depth of the infected lesion in consideration.12 In the current study, LKP was chosen for 2 cases of herpetic and 1 case of bacterial keratitis. Although one herpetic case required optical transplantation, all cases were cured.
In our study, herpetic keratitis was the most common disease in the infection group, whereas Mooren’s ulcer was most frequent in the non-infection group. The original diseases recurred in 4 of 11 eyes in herpetic keratitis (36.7%) and 2 of 5 eyes in Mooren’s ulcer (40%) after the first therapeutic keratoplasty. This is a similar recurrence rate compared to previous studies reporting the recurrence in herpetic keratitis and Mooren’s ulcer.23,34,35 Cyclosporine,36 tacrolimus,37 and oral immunosuppressants34,38 reportedly suppress Mooren’s ulcer after surgery. Some studies mention that LKP, but not AMT, is effective in Mooren’s ulcer.3,36 In our study, KEP was performed in all cases of Mooren’s ulcer using cryopreserved donor corneas. KEP was reported by Kinoshita et al. as the preferred surgical treatment for perforations in Mooren’s ulcers.24 We additionally excised the conjunctiva with a depth of 2–3 mm along the corneal limbs and the corneal tissue around the ulcer. We also removed the immune cells at the bottom of the ulcer (Brown).39 KEP with conjunctival resection was performed in 3 of 5 eyes with Mooren’s ulcers and showed no recurrence. However, the other 2 eyes, in which conjunctival resection was not preformed, resulted in recurrence after keratoplasty. We performed conjunctival resection in both cases and consequently controlled the inflammation with surgical success. KEP in addition to conjunctival resection may suppress inflammation by maintaining the space between the cornea and immune cells of the conjunctiva.
Ti et al. reported that 11 eyes (11.9%) in 92 fungal keratitis cases perforated. Perforation risk factors of fungal keratitis included misdiagnosis, extensive infectious area,11 usage of topical steroids,10 and delayed treatment.40–42 In our study, when the cornea perforated in cases of bacterial and fungal keratitis, we washed out the anterior chamber during the operation.22,43 Furthermore, topical steroids were not used for fungal keratitis for at least 2 weeks postoperatively and only if fungal infiltration was not observed.38,44 Thus, two cases of fungal keratitis achieved anatomical recovery with frozen donor tissue. In one case, the fungal keratitis recurred after therapeutic penetrating surgery but was finally controlled with conservative eye drop treatment. However, one case of fungal keratitis used topical steroids after misdiagnosis as herpes keratitis and had to undergo therapeutic transplantation due to perforation. This case eventually ended up with phthisis bulbus. In the treatment of fungal keratitis, misdiagnosis and early use of steroids may result in detrimental consequences.
The main complications after therapeutic keratoplasty were recurrence of the original disease (7 eyes; 17.1%) and phthisis bulbi (7 eyes; 17.1%). In a previous report, secondary glaucoma and corneal epithelial defect were the main complications.9,27 Iris anterior synechiae preoperatively may induce secondary glaucomas.45 If conservative treatment is not effective and the anterior chamber is not reformed, irreversible iris anterior synechiae may occur. Therefore, if iris anterior synechiae did not return to the original position for more than 2 weeks, we intervened surgically to separate the synechiae to reconstruct the anterior chamber. When in bacterial and fungal keratitis the graft margin was close to the limbus, postoperative inflammation causes trabeculitis and glaucoma.23 In our study, all cases of large grafts resulted in phthisis bulbi, perhaps because the ciliary body function was weakened.
A limitation of the current study is the low number of cases. However, our results show that it is necessary to correctly diagnose the original cause of the disease resulting in corneal perforation and to carefully determine the time of surgical treatment.