Preserved corneal lamellar transplantation for infectious and noninfectious scleral defects

Abstract Rationale : Reinforcement of thinned or necrotizing sclera has been conducted using various materials, including allogeneic sclera, allogenic cornea, amniotic membrane, fascia lata, pericardium, periosteum, and perichondrium. Among them, good outcomes have traditionally been obtained using preserved scleral grafts. However, scleral patch grafts have complications such as graft retraction, thinning, dehiscence, and necrosis. Furthermore, to promote epithelial healing, scleral patch grafting must be accompanied by procedures such as amniotic membrane transplantation (AMT) or grafting using conjunctival flaps or autografts. Recently, acellular preserved human corneas have been used in various ophthalmic surgeries, with emerging evidence supporting its use for treating scleral defects as an option that does not require AMT or conjunctival autografting. We investigated whether corneal patch grafting would show wound healing and tectonic success rate outcomes comparable to those of existing techniques. Patient presentation : Three patients presented with intractable ocular pain. Slit-lamp examination showed marked scleral thinning at the nasal side. Diagnosis : Scleral thinning progressed with conservative treatment; microbial staining and culturing were performed. Infectious or non-infectious scleritis was diagnosed according to slit-lamp examination and microbial culture results. Interventions : A preserved corneal lamellar patch was grafted at the scleral thinning area. Outcomes All patients achieved tectonic success with reduction of inflammation following corneal patch grafting. Two patients achieved complete re-epithelialization within 7 days, while 25 days were required for the third patient. No patients experienced graft thinning, rejection, or infection. Lessons : Our report suggests the feasibility of using acellular preserved human cornea patch grafts to reinforce inflammatory scleral defects and obtain successful outcomes in terms of wound healing. This technique shows a comparable tectonic success rate and superior effect on scleral defect healing without the need for adjunctive AMT or conjunctival autografting.


Introduction
Infectious or noninfectious scleral necrosis with calcium deposition could occur after pterygium removal, trauma, idiopathic systemic vasculitis, or retinal detachment surgery. [1] Severe scleral thinning with exposed calcium or uveal tissue in the defect area can induce secondary infection or necrotizing scleritis and leave the eyeball vulnerable to minor trauma. [2] To prevent these adverse events, scleral reinforcement is performed to cover the thinned sclera using different materials, including allogeneic sclera, amniotic membrane, fascia lata, pericardium, periosteum, and perichondrium. [3][4][5] Among them, good outcomes have traditionally been obtained using preserved scleral grafts. However, these are associated with complications such as graft retraction, thinning, dehiscence, and necrosis. [6] Furthermore, scleral graft transplantation must be accompanied by amniotic membrane transplantation (AMT) to promote epithelization over the scleral or conjunctival graft, [7,8] which increases surgical time. [9] Acellular preserved human corneal tissue can be transplanted to the scleral defect area without the need for AMT or conjunctival grafting, which has been shown to reduce inflammation and accelerate wound healing in rabbits. [10] Compared with the sclera, the cornea has a basement membrane and collagen fibrils that are arranged compactly, which is expected to be beneficial for wound healing and graft survival. [11] We report on 3 cases of infectious or noninfectious scleral defects with successful transplantation of acellular preserved corneal lamellar grafts followed by rapid wound healing and inflammation reduction. This technique seems to have an effect on scleral graft healing comparable or superior to that of adjunctive AMT or conjunctival autograft.

Case 1
A 74-year-old female underwent right-eye pterygium surgery approximately 13 years ago. She presented to our ophthalmology department with a six-month history of right ocular pain (Table 1). Her right-eye best corrected visual acuity (BCVA) was 20/20. Marked scleral thinning with a 4.5 Â 4.5 cm calcium plaque was observed medially on slit-lamp examination (Fig. 1A). No organism was isolated on microbial staining and culture. The patient was diagnosed with noninfectious scleritis following pterygium removal surgery. A preserved corneal lamellar patch (Halo; Eversight Inc., Palo Alto, CA) was grafted after calcium plaque excision. At 1 week postoperatively, ocular surface epithelialization was complete and inflammation was diminished. At 1 month postoperatively, vascularization had partially progressed with regression of inflammation (Fig. 1B).
One year postoperatively, the graft had been vascularized and a stable surface had been maintained (Fig. 1C). Her BCVA remained at 20/20.

Case 2
A 66-year-old female with ocular pain was referred to our department (Table 1). Her right-eye BCVA was 20/20. On slitlamp examination, scleral thinning with infection and a 5 mm Â 3.2 mm exposed calcium plaque was observed on the nasal aspect of the right eye (Fig. 1D). Although the patient received anti-inflammatory medication before referral, scleral thinning had progressed. Bacillus species was isolated on microbial staining and culture. The patient was diagnosed with infectious scleritis with exposed calcium plaque. The calcium plaque was excised, and a preserved corneal lamellar graft (Halo; Eversight Inc., Palo Alto, CA) was transplanted. One week postoperatively, with topical application of 0.5% moxifloxacin (Vigamox, Alcon, TX), the graft surface was fully epithelized and her BCVA was 20/20 ( Fig. 1E). One month postoperatively, the graft surface was stable and there was no infection or inflammation (Fig. 1F). Subconjunctival haemorrhages were noted after suture removal (Fig. 1F).

Case 3
An 82-year-old male visited our hospital with a three-month history of severe pain and decreased visual acuity in the left eye (Table 1). At the initial visit, his BCVA was 4/20. Slit-lamp examination revealed diffuse scleral infection, nasal scleromalacia with a large calcified plaque, an inferotemporal scleral nodule, and nasal corneal stromal oedema with endothelial infiltration. Severe anterior chamber inflammation was also observed. The nodule was filled with pus originating from the nasal side. Culture revealed Paecilomyces and Bacillus species. The patient was diagnosed with fungal scleritis with bacterial infection. Hourly topical administration of 0.5% moxifloxacin (Vigamox, Alcon  Laboratories, Inc., Fort Worth, TX), 2.5% fortified vancomycin, 5% ceftazidime, and 1% voriconazole, as well as oral administration of 200 mg voriconazole twice daily and 400 mg moxifloxacin once daily was performed. Five weeks later, although the infection was partially controlled, scleral necrosis had worsened compared to the initial visit. The defect size was 5 Â 8 mm with iris prolapse at the inferonasal limbus that extended to the scleral defect (Fig. 1G). After calcium plaque (4 Â 9 mm) excision, the patient underwent tectonic keratoplasty using a full thickness corneoscleral graft and patch grafting using preserved corneal tissue (Halo; Eversight Inc., Palo Alto, CA). Twenty five days postoperatively, inflammation was reduced and complete graft epithelialization was observed (Fig. 1H). Six months postoperatively, the graft was vascularized and stable (Fig. 1I). Although his BCVA was only light perception, infection had subsided and the eyeball was saved.

Discussion
Surgical management of infectious or noninfectious scleritis with severe thinning remains challenging, and scleral wall reinforcement has been attempted using various materials. [3][4][5]12] We used an acellular preserved human cornea patch graft to manage scleral thinning with inflammation and obtained successful wound healing and inflammation reduction outcomes. In a retrospective report of 13 cases of necrotizing scleritis, scleral thinning, or dehiscence by Sangwan et al, the tectonic success rate was 76.9% and 3 complications were noted (endophthalmitis, graft necrosis, and graft dehiscence). In addition, re-epithelization occurred after an average of 3 to 4 weeks. [6] Oh et al reported that the scleral graft remained intact and no recurrence was observed in 8 patients with noninfectious scleromalacia. Re-epithelization was observed within 7 days in 7 of those patients; 6 weeks were required for re-epithelization in the remaining patient. [9] Kim et al reported a high success rate of grafting using autologous perichondrium with AMT in 17 out of 18 eyes (94.4%) at 6 months postoperatively. However, their surgical technique necessitates harvesting the perichondrium from the tragus prior to AMT, which increases surgical time. [5] A literature review reveals that our tectonic success rate and reepithelialization time were comparable to those previously reported in studies of scleral grafting (Table 2); moreover, there were no adverse events. The shorter surgical time may be a benefit of our technique over scleral grafting combined with adjunctive surgeries such as AMT, conjunctival autograft/flap use, or perichondrial harvesting. Given that corneal type 4 collagen facilitates corneal epithelial adhesion, faster wound healing may occur with corneal grafting. [13] In Case 3, epithelialization took a relatively long time (25 days). Considering that it was a case of fungal infection with a poor prognosis, this could be regarded as a relatively good outcome. The patient's decreased visual acuity was due to corneal opacity and iris synechiae obscuring the pupil.
Several studies of acellular or cellular corneal graft use for scleral reinforcement using various surgical techniques have been published (Table 2); some report acceptable effectiveness of corneal patch grafting in patients with scleral thinning after pterygium surgery, penetrating keratoplasty, or radiotherapy. [12,[14][15][16][17] However, they used corneal grafts from fresh corneas or donated whole corneas after Descemet stripping endothelial keratoplasty. Two reports of successful tectonic outcome using acellular corneal graft in patients with scleritis following strabismus surgery have been published. [18,19] The rate of epithelialization was mentioned in only one study. [18] Taken together, this study supports the evidence that preserved corneal lamellar grafting may be feasible for scleral defects.
No study directly compares the efficacy of corneal and scleral grafts for treating scleral defects. However, we can infer and compare the effects based on studies in patients who underwent glaucoma valve surgery with corneal grafting. These studies showed comparable tectonic results between corneal and scleral grafts, and they found that surgeons used corneal grafts 3.8 times more frequently than scleral grafts. [20,21] In addition, evidence suggests that acellular preserved corneal grafting is effective for reducing inflammation and promoting wound healing in rabbits. [10] This study was limited by the small number of patients and short follow-up duration. Nevertheless, it provides evidence that acellular preserved corneal grafting promotes wound healing, has comparable tectonic success rates to those of traditionally used  [14] 20 Infectious scleritis Conjunctival flap NA 14 95 5 ‡ Kymionis GD [15] 1 Necrotizing scleritis None 2 12 100 0 Lin HC [16] 1 Infectious scleritis Conjunctival flap NA 24 100 0 Ramos-Esteban [17] 1  techniques, and may have the advantage of a shorter surgical time in the treatment of scleral defects. Therefore, surgeons should consider acellular preserved cornea grafting as an option for the treatment of infectious or noninfectious scleral defects.