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Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 388-390

Hyperacute stromal and endothelial rejection in therapeutic penetrating keratoplasty with residual intra-stromal crystalline deposits

1 Department of Cornea and Refractive Surgery, Sankara Nethralaya, Medical Research Foundation, Chennai- 600 006, Tamil Nadu, India
2 Department of Uvea, Sankara Nethralaya, Medical Research Foundation, Chennai- 600 006, Tamil Nadu, India
3 Department of Optometry, Sankara Nethralaya, Medical Research Foundation, Chennai- 600 006, Tamil Nadu, India

Date of Submission19-Sep-2021
Date of Acceptance06-Nov-2021
Date of Web Publication13-Apr-2022

Correspondence Address:
Bhaskar Srinivasan
Sankara Nethralaya, Medical Research Foundation, 18, College Road, Chennai - 600 006, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_2443_21

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Stromal rejection is rare and uncommonly seen in its pure form. We report a case of hyperacute stromal rejection followed by endothelial rejection post-therapeutic penetrating keratoplasty (PK) done for fungal keratitis. The rejection episode responded to steroids with a clearing of the graft. Residual mid to deep intra-stromal crystalline deposits remained at the area of stromal rejection, which remained stationary for a follow-up period of 1 year. The patient underwent Anterior segment optical coherence tomography (AS-OCT) to demonstrate the condition objectively.

Keywords: Endothelial rejection, hyperacute stromal rejection, intra-stromal crystalline deposits

How to cite this article:
Agarwal M, Srinivasan B, Iyer G, Agarwal S, Sudharshan S, Janarthanam JB, Rajagopal R. Hyperacute stromal and endothelial rejection in therapeutic penetrating keratoplasty with residual intra-stromal crystalline deposits. Indian J Ophthalmol Case Rep 2022;2:388-90

How to cite this URL:
Agarwal M, Srinivasan B, Iyer G, Agarwal S, Sudharshan S, Janarthanam JB, Rajagopal R. Hyperacute stromal and endothelial rejection in therapeutic penetrating keratoplasty with residual intra-stromal crystalline deposits. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 May 18];2:388-90. Available from: https://www.ijoreports.in/text.asp?2022/2/2/388/342957

Allograft rejections are the leading cause of corneal graft failure.[1] Presence of more than two-quadrant vascularization in the recipient, large/eccentric grafts closer to the limbus, ongoing inflammation/infection, and previously failed grafts secondary to rejection predispose to higher graft rejection. Allograft rejection can be epithelial, hyperacute/chronic stromal, endothelial, or combined stromal-endothelial rejection.[2] Pure form of hyperacute stromal rejection is rarely reported after penetrating keratoplasty (PK) and often associated with immediate or simultaneous endothelial rejection.[3],[4]

  Case Report Top

A 38-year-old male (unaided vision 20/20 in both eyes) presented with a 20-day history of redness, itching, and pain in the right eye following caterpillar hair injury. The right eye had a stromal infiltrate with grade-1 anterior chamber cells. Ultrasound biomicroscopy showed presence of a hyper-reflective fine line in the stroma suggestive of caterpillar hair. Rest of the ocular examination was normal. Patient was started on a short course of 1% prednisolone acetate topically with 0.03% tacrolimus ointment at nighttime, and the lesion responded. Inflammation flared on stopping steroids. Therefore, the patient self-medicated and presented after 2 months with deep stromal infiltrates and corneal thinning near the limbus [Figure 1]a. Corneal scraping was positive for fungal filaments. Topical and oral antifungals were started. However, therapeutic PK (9.50 mm eccentric graft) was performed due to impending perforation.
Figure 1: Slit-lamp image of right eye showing: (a) deep stromal infiltrates nasally with feathery appearance and corneal thinning from 2 o'clock to 4 o'clock position near the limbus, (b) clear donor cornea with few DM folds 2 weeks postoperatively, (c and d) severe white focal stromal edema in the superonasal graft with focal congestion and vascularization in same quadrant with clear inferior cornea 3 weeks postoperatively, (e) few inferior pigment deposits on endothelium

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Topical antifungals were continued postoperatively. Steroids were withheld in the early postoperative period. At 2 weeks postoperatively, the graft was reasonably clear with few Descemet's membrane (DM) folds [Figure 1]b. There was no evidence of infection. Antifungals were reduced, and the patient was reviewed in a week, with contemplation to start steroids. At third-week visit, the patient presented with severe white focal stromal edema involving the superonasal graft with focal congestion and vascularization in the same quadrant [Figure 1]c and [Figure 1]d. The inferior cornea had few endothelial pigment deposits, but remaining cornea was reasonably clear [Figure 1]e. AS-OCT revealed severe stromal edema (pachymetry 1266 microns) with isolated hyperreflective opacities at the endothelial level, not appreciated clinically, probably suggestive of early endothelial rejection [Figure 2]. A clinical diagnosis of hyperacute stromal rejection was made, and the patient was started on topical 1% prednisolone acetate hourly and systemic steroids. By the third day, the superonasal stromal edema reduced; however, the lower part of the graft that was clear earlier now showed stromal edema, DM folds, and pigmented keratic precipitates (KPs), indicating a resolving endothelial rejection [Figure 3]a and [Figure 3]b. The stromal-endothelial rejection responded to medical management. At 1-month follow-up, the graft was clear except for mid to deep stromal crystalline deposits at the area of stromal rejection and presence of pigmented KPs at the endothelial rejection site [Figure 3]c and [Figure 3]d. The stromal deposits didn't affect the vision, and the best spectacle-corrected visual acuity (BSCVA) was 20/20 (3 DCylx65°). The patient was maintained on topical steroids and tacrolimus. At 1 year postoperatively, BSCVA was maintained at 20/20, N6 with persistence of stromal crystalline deposits [Figure 4].
Figure 2: AS-OCT image during the hyperacute stromal rejection episode showing severe corneal stromal edema with pachymetry value of 1266 microns and isolated hyperreflective opacities at endothelial level

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Figure 3: Slit-lamp picture in diffuse illumination and slit beam section (a and b) on day 3 of treatment showing reduced superonasal stromal edema with inferior stromal edema, DM folds and pigmented keratic precipitates, (c and d) at 1-month follow-up showing clear graft with stromal crystalline deposits in the area of the previous stromal rejection and presence of pigmented keratic precipitates in the area of endothelial rejection

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Figure 4: Slit lamp image of the right eye in diffuse and slit illumination (a and b) at 1 year postoperatively showing persistence of the stromal crystalline deposits

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  Discussion Top

Graft rejection is an immune-mediated process limited to the graft. It starts around 3 weeks in a successful clear graft.[2] Although endothelial rejection is the commonest cause of allograft rejections in PK, isolated stromal rejection or combined stromal-endothelial rejections can occur; however, hyperacute stromal rejection occurring within a month of surgery is rare and seen in inflamed eyes or previously failed grafts.[2],[5] Stromal rejection starts close to the periphery and migrates towards the center within 24–48 hours; clinical features include sectoral or global stromal infiltration with or without subsequent neovascularization.[4],[5] Rarely stromal rejection can result in corneal melt/necrosis.[4]

Yenerel et al.[6] described acute graft rejection on high-resolution AS-OCT as stromal thickening with undulation of the posterior corneal surface, as was in our case at third week, opposed to chronic graft failure showing stromal thickening with smooth posterior surface. In our case, undulation of DM was noted in both stromal and endothelial rejection area, but stromal rejection site edema was much higher than endothelial rejection site edema. Stromal rejection responded well to steroids with clearing of the cornea by third day. Endothelial rejection took a bit longer to respond. To the best of our knowledge, clinical and OCT documentation of both stromal and endothelial rejection in PK is not reported.

At 1-month postrejection, mid to deep stromal crystalline deposits were only noted in the previous stromal rejection area and not in endothelial rejection area. Mason et al.[7] have described these in their series of five eyes. Studies have demonstrated that immune-complexes can precipitate in stroma and clinically appear as needle-like polychromatic crystals involving various depths. Though infrequent, during acute rejection, antigen–antibody excess leads to complex precipitates that are once seen haze with edema clear. In our patient, these crystals were unilateral, seen shortly after the resolution of stromal edema, and not seen in the host stroma. The crystals were visually insignificant and stationary over the 1-year follow-up period. Our case was high risk due to ongoing inflammation, infection, and a large eccentric graft. Steroids were withheld in the initial postoperative period, given the fungal etiology. These factors probably predisposed the graft to a hyperacute rejection.

  Conclusion Top

In conclusion, stromal rejection during early postoperative period can be seen in high-risk grafts. A high index of suspicion of stromal rejection should be made when there is sudden severe stromal edema in a previously clear graft. Stromal rejection can be accompanied by endothelial rejection, and appropriate treatment can restore visual acuity. Severe stromal rejection can result in crystalline corneal deposits.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Krachmer JH, Mannis MJ, Holland EJ. Cornea: Fundamentals. Diagnosis and Management. Mosby Elsevier; 2011.  Back to cited text no. 1
Panda A, Vanathi M, Kumar A, Dash Y, Priya S. Corneal graft rejection. Surv Ophthalmol 2007;52:375-96.  Back to cited text no. 2
Tan DT, Janardhanan P, Zhou H, Chan YH, Htoon HM, Ang LP, et al. Penetrating keratoplasty in Asian eyes: The Singapore corneal transplant study. Ophthalmology 2008;115:975-82.  Back to cited text no. 3
Khodadoust AA, Silverstein AM. Transplantation and rejection of individual cell layers of the cornea. Invest Ophthalmol 1969;8:180-95.  Back to cited text no. 4
Olson EA, Tu EY, Basti S. Stromal rejection following deep anterior lamellar keratoplasty: Implications for postoperative care. Cornea 2012;31:969-73.  Back to cited text no. 5
Yenerel NM, Kucumen RB, Gorgun E. The complementary benefit of anterior segment optical coherence tomography in penetrating keratoplasty. Clin Ophthalmol 2013;7:1515-23.  Back to cited text no. 6
Mason CM, Sugar A, Meyer RF. Intrastromal crystalline deposits following corneal graft rejection. Cornea 1984;3:89-94.  Back to cited text no. 7


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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