Stromal graft rejection after deep anterior lamellar keratoplasty at a tertiary care center

Abstract

PURPOSE:

To evaluate the characteristics and outcomes of stromal rejection after deep anterior lamellar keratoplasty (DALK) at a tertiary care center in Saudi Arabia.

METHODS:

The clinical records of 42 patients who underwent DALK between January 2019 and December 2023 were reviewed to identify patients who had experienced stromal rejection. Those patients were analyzed in terms of biodata, indications for surgery, graft size, subjective and objective clinical findings, treatment courses, and follow-ups.

RESULTS:

Of the 42 cases of DALK conducted during the study in our center, 3 (7.1%) experienced graft rejection between postoperative months 8 and 18. The mean age of patients with rejection at presentation was 30.6 years, compared to 33.5 years for those without rejection. The mean follow-up durations were 16.6 months for patients with rejection and 25.7 months for patients without rejection. All patients started intensive topical prednisolone acetate 1% (half hourly to hourly) on first presentation, and one had a pulse of intravenous methylprednisolone. A complete recovery was observed in all patients after 1–2 weeks.

CONCLUSION:

While DALK offers significant advantages over full-thickness corneal grafting, graft rejection remains a potential complication. Early presentation and timely treatment of rejection after DALK carry a good prognosis and can prevent graft failure.

INTRODUCTION

Deep anterior lamellar keratoplasty (DALK) is a surgical procedure that involves removal of the diseased corneal stroma. This procedure exposes the Descemet’s membrane, upon which a full-thickness donor cornea, excluding the Descemet’s membrane and endothelium, is transplanted.[1] Therefore, DALK potentially reduces the risk of graft rejection compared to penetrating keratoplasty (PK), as it eliminates the potential for endothelial rejection, which is the primary cause of graft failure following PK.[2]

Herein, we reviewed the records of all cases from our center who underwent DALK during the 5 years between January 2019 and December 2023. We analyzed the cases of graft rejection that were successfully treated by topical steroids with or without an intravenous (IV) pulse steroid.

METHODS

This retrospective observational study included all DALK cases performed at our center between January 2019 and December 2023. The study was registered, and approval was obtained from the institutional review board (IRB).

The graft rejection cases were identified and analyzed in terms of clinical and surgical aspects. The clinical presentations of the cases of rejection were compared to the findings reported in similar published studies.[3,4]

RESULTS

Of the 42 patients included in this study, 3 (7.1%) patients had an episode of graft rejection. The mean age for those patients who had rejection at the rejection presentation time was 30.6 years (range, 19–39 years), whereas the mean age for those who had no rejection was 33.5 years (range, 17–49 years) [Table 1]. The mean follow-up duration was 16.6 months for patients with rejection and 25.7 months for patients without rejection.

Table 1.

Demographics of the rejection and nonrejection groups

	DALK with rejection (n=3)	DALK with no rejection (n=39)
Males	1	19
Females	2	20
Mean age (years)	30.6	33.5
Mean follow-up duration (months)	16.6	25.7

DALK: Deep anterior lamellar keratoplasty

The indication for DALK in the rejection cases was keratoconus [Table 2]. The mean time of rejection presentation after surgery was 11.6 months (range, 8–18 months). The DALK technique used in all patients in the rejection group was the big bubble technique, with a host trephine size between 7.75 and 8.00 mm and a donor trephine size between 8.25 and 8.5 mm.

Table 2.

Cases of rejection after deep anterior lamellar keratoplasty

	Case 1	Case 2	Case 3
Age (years)	34	19	39
Gender	Male	Female	Female
Indication for surgery	Keratoconus	Keratoconus	Keratoconus
Presentations after surgery (m)	8	9	18
DALK technique	Big bubble	Big bubble	Big bubble
Topical steroids at presentation	None	None	None
Postoperative steroid use duration (months)	7	8	9
Length of time between presentation and stopping steroids	4 weeks	5 weeks	9 months
BCVA at rejection presentation	20/100	Counting fingers at 4 feet	Counting fingers at near face
BCVA after recovery	20/60	20/30	20/40
Special consideration	Steroids responder	Poor compliance	-
Host trephine size (mm)	8.00	7.75	8.00
Graft size (mm)	8.5	8.25	8.5
Recovery	Yes	Yes	Yes
Recovery duration (days)	4	6	7

DALK: Deep anterior lamellar keratoplasty, BCVA: Best-corrected visual acuity

All the patients who had a rejection episode presented when they had already discontinued the topical steroid treatment, and the duration of use ranged from 7 to 9 months. The rejection presentation started 1–9 months after discontinuation of the topical steroid. All the rejection cases presented with pain, photophobia, decreased vision, conjunctival injection, and diffuse corneal edema; one case also presented with subepithelial corneal infiltrates and superior peripheral corneal neovascularization [Figures 1a, b and 2a].

Figure 1.

(a) Case 1: Slit-lamp view (diffuse) showing superior peripheral vascularization and edema of the graft at presentation. (b) Case 1: Slit-lamp view showing subepithelial infiltrates at presentation. (c) Case 1: Slit-lamp view (diffuse) showing clear graft 1 week after treatment

Figure 2.

(a) Case 2: Slit-lamp view (diffuse) showing edema of the graft at presentation. (b) Case 2: Slit-lamp view (diffuse) showing clear graft 1 week after treatment

One of the rejection cases was a steroid responder, and he was managed with topical aqueous suppressant and a more rapid tapering of the topical steroid, which was discontinued 7 months after the surgery. Another patient reported poor compliance with the topical steroid.

All the rejection cases completely recovered with topical prednisolone acetate 1% (half hourly to hourly), and one of them also received a 500 mg pulse of IV methylprednisolone [Figures 1c and 2b]. The mean recovery period was 5.6 days (range, 4–7 days).

DISCUSSION

The occurrence of graft rejection after DALK is considered low, especially when compared to rejection following PK.[3,5] Kubaloglu et al. reported 4 (1.6%) cases of stromal rejection out of 241 eyes that underwent DALK, and all the patients completely recovered with the topical treatment.[6] The rejection rates reported in the literature ranged from 0% to 23.8%, with a mean of 5.4%, and the complete recovery from rejection ranged between 89.5% and 100%, with a mean of 98.7% [Table 3]. This could emphasize and align relatively with our results in terms of low risk of DALK rejection and good response to treatment. However, Saini et al.[5] and Soong et al.[7] reported irreversible loss of vision after DALK due to presumed stromal graft rejection in 1 (1.9%) of 52 eyes, and 2 (1.4%) of 138 eyes, respectively. Other reported patterns of graft rejection after DALK have included epithelial and subepithelial rejection, as was evident in Case 1 as subepithelial infiltrates in the present study [Figure 1]. Arslan et al. and Feizi et al. reported 20 graft rejections in 208 patients after DALK during the first 9–12 months, while in our study 2 out of the 3 rejection cases presented during the first 9 months after the surgery, indicating the importance of close observation and treatment compliance during the first postoperative year.[8,9]

Table 3.

Literature review of graft rejection following deep anterior lamellar keratoplasty

References	Total number of eyes	Number of eyes with rejection	Rejection rate (%)	Number of eyes with complete recovery	Recovery rate (%)	Rejection treatment
Kasamatsu et al.[4]	464	24	5.2	17	89.5	Topical steroids
Kodavoor et al.[10]	484	3	0.61	3	100	Topical prednisolone 1% hourly
Kubaloglu et al.[6]	241	4	1.6	4	100	Topical prednisolone acetate
Arslan et al.[8]	79	2	2.5	2	100	Topical steroids
Feizi et al.[9]	129	18	13.9	18	100	Topical betamethasone 0.1%
Wylegała et al.[11]	53	0	0	-	-	-
Fontana et al.[12]	78	2	2.5	2	100	Topical dexamethasone 0.1%
Sarnicola et al.[13]	660	26	3.9	26	100	Topical steroids
Javadi et al.[14]	42	10	23.8	10	100	Topical steroids

No consensus has yet been reached regarding the optimal duration and dosage of topical steroids after keratoplasty. Kasamatsu et al. found that patients who experienced rejection after DALK (24 eyes) had a significantly shorter duration of topical steroid use compared to those without rejection (464 eyes).[4] Javadi et al. reported the highest rejection rate among the other studies with a rejection rate of 23.8% (10 eyes out of 42), this could be attributed to the short duration of topical steroids postoperatively (mean 98.4 days).[14] This finding could support our study findings in two of our patients who experienced a rejection episode following an earlier-than-usual discontinuation of the topical steroid due to ocular hypertension and poor compliance. Thus, a slower tapering, i.e. over 9–12 months, of topical steroid use following DALK, especially in high-risk cases, might lower the risk of rejection.

Other reported risk factors for graft rejection include peripheral corneal neovascularization, loose sutures, vernal keratoconjunctivitis, and ocular surface disease; however, none of these were present in our cases of rejection.[9,15] Hence, it is crucial to address these factors, as they may require an extended steroid course and more frequent follow-up.

The primary cause of graft failure following PK is rejection, whereas this is not the case for DALK.[16] Sarnicola et al. studied 660 eyes post-DALK, finding that 4 cases (0.6%) resulted in graft failure due to graft infection and late endothelial failure, with none attributed to rejection.[13] This may indicate the superiority of DALK over PK, particularly in high-risk cases.

CONCLUSION

Our study’s findings corroborated those of the articles we reviewed. Post-DALK graft rejection remains a potential complication; however, the risk of rejection can be minimized through longer steroid tapering, patient compliance, and closer monitoring during the 1^st year.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.