Late central graft detachment due to double endothelial layer after repeat Descemet membrane endothelial keratoplasty

Purpose To report late central graft detachment after repeat Descemet membrane endothelial keratoplasty (DMEK) without visual reduction. Observations A 71-year-old patient with Fuchs’ endothelial corneal dystrophy received a DMEK in his left eye. At 11 month post-operatively, a subtotal graft detachment was noted. Due to increasing corneal edema with vision loss, the first DMEK was removed and a repeat-DMEK was performed. At four months post repeat-DMEK, the graft was fully adherent to the posterior stroma. There was no significant corneal edema, and the best corrected visual acuity was 20/25. At 16-months after repeat-DMEK, a central graft detachment was noted, but there was no concurrent corneal edema or any loss of visual acuity. The mean density of the central endothelial cells was measured at 842 cells/mm2. Given the lack of corneal edema, visual reduction or subjective visual complaint, the graft detachment was followed-up for up to 20-months post repeat-DMEK with no further intervention, where the central cornea remained clear. Conclusions and Importance To our knowledge, this is the first report of a central repeat-DMEK graft detachment that occurred 16 months after surgery despite initial attachment. Interestingly, there was no concurrent corneal edema or vision reduction. We describe a potential mechanism for clear central cornea in the presence of a central graft detachment after repeat-DMEK.


Introduction
In patients with Fuchs' endothelial corneal dystrophy (FECD), a progressive reduction of endothelial cell density leads to inadequate dehydration of corneal stroma, ultimately causing corneal edema and visual impairment. 1 Descemet membrane endothelial keratoplasty (DMEK) is currently the treatment of choice for FECD patients. By replacing the diseased endothelium with a functioning endothelial layer, the fluid transport is reconstituted, and the corneal clarity can be restored. 2,3 Despite high success rates and good visual outcomes reported after DMEK, postoperative success can be compromised by a number of complications. 4,5 In particular, previous studies have reported peripheral graft detachment to occur in 26-56% of cases. 6,7 Without further treatment, there is a high risk of vision loss as it may progress to detach completely. Thus, in cases of peripheral or complete graft detachment, a re-bubbling or repeat-DMEK may need to be performed. 7 Graft detachments are typically observed in the early postoperative period, which highlights the importance of close follow-up examinations following the surgery. To our knowledge, a graft detachment occurring numerous months after surgery has not been reported before, particularly a detachment that only involves the graft center. This case report presents a case of a late central graft detachment occurring after repeat-DMEK in an eye that previously underwent DMEK for FECD.

Case report
A 71-year-old White male presented to our department with blurry vision in his left eye. He had previously undergone DMEK in this eye 11 months ago for corneal decompensation due to FECD. Other previous ocular history was unremarkable except for cataract surgery on both eyes more than 10 years ago. His systemic comorbidities included myasthenia gravis, rheumatoid arthritis, and obstructive sleep apnea syndrome.
The left eye showed a best-corrected visual acuity (BCVA) of 20/200, and the slit-lamp examination revealed a diffuse corneal edema involving the optical axis. Optical coherence tomography (OCT) demonstrated a subtotal DMEK graft detachment (Fig. 1A) and a central corneal thickness of 552 μm. Given the clinically significant corneal decompensation in the setting of a subtotal graft detachment, the patient was advised to undergo repeat DMEK.
The repeat-DMEK was performed with no intraoperative complications and the new graft was completely attached to the stromal surface under 20% SF6 gas tamponade. Both the slit-lamp and the anteriorsegment OCT confirmed a fully adherent graft position ( Fig. 2A) at 2days postoperatively. As shown in Fig. 3, the BCVA improved to 20/ 60 at 8-days postoperatively.
At 1-and 4 months after surgery, the graft was still fully attached to the host stroma and the BCVA had improved to 20/25. The central corneal thickness was 489 μm.
When the patient followed up at 16-months postoperatively, however, a central graft detachment was observed (Fig. 1B). A broad slitlamp beam demonstrated a detached area of approximately 4.5 mm only in the central cornea (Fig. 1C). The BCVA was 20/20. There was no clinical corneal edema or corneal scarring. The anterior-segment OCT confirmed the central graft detachment with peripheral graft still fully attached to the corneal stroma (Fig. 2B). Central corneal thickness was 499 μm. The height of graft detachment was measured at 1.2 mm.
Given the good BCVA and the lack of any subjective visual complaints, we decided against a surgical intervention and followed-up in 4 months. At 20-months after repeat-DMEK, the magnitude of central graft detachment remained stable with consistent diameter and height of the detachment (Fig. 2C), and there were still no signs of corneal edema. The BCVA also remained at 20/20 and the central corneal thickness was 487 μm. A specular microscope (CEM-530, NIDEK, Gamagori, Aichi, Japan) was used to measure the endothelial cell density in the central cornea, which showed a mean endothelial cell count of 841.7 ± 57.6 cells/mm 2 . The HRT3 Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany), which is widely used to analyze the depth and composition of corneal layers, confirmed the location of the endothelial cells in the central posterior corneal stroma. Given the clinically stable situation with no visual impairment, we decided to continue observation with no further surgical intervention.

Discussion
DMEK graft detachment generally occurs in the early postoperative period and is often accompanied by vision loss due to increasing corneal edema in the area of detachment. 8,9 In our case, however, the repeat-DMEK graft not only detached more than 3 months after surgery, but also only occurred in the central cornea with no signs of concurrent corneal edema or loss of visual acuity.
It is unclear which exact mechanism led to late graft detachment that only involves the central cornea. In our case, a subtotal graft detachment was first observed at 11-months after the initial DMEK. As the patient had failed to follow-up between 1 and 11 months after the initial DMEK, it is unknown for how long the graft had remained detached in this eye as shown in Fig. 1A. However, there seems to have been a physical contact between the endothelial side of the detached graft tissue and the central posterior stroma, leading us to hypothesize that this may have (caption on next column) Immediately after repeat-DMEK, the migrated endothelial cells on central posterior stroma, together with peripheral endothelial cells from the second DMEK graft, then presumably began to dehydrate the edematous cornea. This is reflected in the gradual improvement of BCVA and corneal clarity at 4-months post repeat-DMEK, which is in alignment with a report by Lazaridis et al. who observed a recovery of corneal clarity at 3-months following DMEK. 10 During this process, the stromal fluid transported by the migrated endothelial cells on central posterior stroma likely began to "push" the second DMEK graft away, leading to central detachment of the graft and progressive fluid accumulation between the endothelial cells and the second DMEK graft.
In such a case, one would expect the gradual fluid "pouch" above the area of graft detachment to continue to increase and ultimately cause a total graft detachment. Interestingly, however, the size of graft detachment remained unaltered. One possible mechanism may be that the healthy endothelial cells residing in central repeat-DMEK graft also transport a similar amount of fluid from the accumulating fluid pouch, thereby establishing a certain balance in the amount of fluid that is being transported 1) from the central corneal stroma into fluid pouch and 2) from the fluid pouch into the anterior chamber (Fig. 4).
Surely, a re-bubbling may be a possible option to treat such a graft detachment. However, a re-bubbling in the setting of such a central graft detachment could apply pressure on the central fluid accumulation and lead to a further increase in graft detachment. A third DMEK may also be a possibility. However, the central corneal clarity as well as the lack of visual loss or complaints dissuaded us to perform a third corneal transplantation.
In conclusion, late central graft detachment can occur after repeat-DMEK, possibly due to endothelial cells that migrate from the first DMEK tissue onto the host posterior stroma. This suggests that stromal polishing may be useful when performing a repeat endothelial keratoplasty to remove all residual migrated endothelial cells. Central graft detachments with no associated corneal edema or visual loss can be observed with no surgical intervention. Future studies are necessary to confirm the mechanism of late repeat-DMEK graft detachment described herein.

Patient consent
Written informed consent for publishing personal information and case details was obtained from the patient. A copy of the written consent is available upon reasonable request.

Funding
No funding or grant support.

Declaration of competing interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ramin Khoramnia -Heidelberg Engineering -Lecture fee The