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Year : 2021  |  Volume : 1  |  Issue : 3  |  Page : 476-478

Medical device composed of amniotic membrane inhibits the rapid progression of acute calcareous degeneration caused by ocular graft-versus-host disease: Case report

1 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
2 Department of Ophthalmology, National Taiwan University Hospital; Advanced Ocular Surface and Corneal Nerve Regeneration Center, National Taiwan University Hospital; Department of Ophthalmology, College of Medicine, National Taiwan University, Taipei, Taiwan

Date of Submission05-Aug-2020
Date of Acceptance29-Jan-2021
Date of Web Publication02-Jul-2021

Correspondence Address:
Dr. Wei-Li Chen
Department of Ophthalmology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_2540_20

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A 27-year-old man who underwent hematopoietic stem cell transplantation (HSCT) for the treatment of T-cell acute lymphoblastic leukemia presented with bilateral persistent corneal erosions. Acute calcareous deposition was later found in both eyes, and the ocular condition deteriorated rapidly. Active treatment with topical lubricants, topical anti-inflammatory agents, autologous serum, and punctal plug insertion were applied but in vain. Amniotic membrane (Prokera) was then applied in both eyes, and the corneal erosion and ocular inflammation improved rapidly. The intrastromal calcium deposition remained and did not progress.

Keywords: Acute calcareous degeneration, cornea, ocular GVHD

How to cite this article:
Wan YJ, Ma IH, Chang HW, Chen WL. Medical device composed of amniotic membrane inhibits the rapid progression of acute calcareous degeneration caused by ocular graft-versus-host disease: Case report. Indian J Ophthalmol Case Rep 2021;1:476-8

How to cite this URL:
Wan YJ, Ma IH, Chang HW, Chen WL. Medical device composed of amniotic membrane inhibits the rapid progression of acute calcareous degeneration caused by ocular graft-versus-host disease: Case report. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Jul 28];1:476-8. Available from: https://www.ijoreports.in/text.asp?2021/1/3/476/319996

Over the past two decades, allogeneic hematopoietic stem cell transplantation (HSCT) has become the promising curative therapy for hematologic and lymphoid malignancies.[1] However, ocular graft-vs-host disease (GVHD) remains one of the major complications. There are two types of ocular GVHD: acute (postoperative day 1–100) and chronic (postoperative period > 100 days).[2] The presentation of ocular GVHD includes conjunctival inflammation, keratoconjunctivitis sicca (KCS), corneal ulceration, cataract, glaucoma, and retinitis. In severe cases, melting of the cornea leading to corneal perforation may occur even under intensive treatment.[1],[3] Very rarely, acute calcareous degeneration, a disease caused by calcium deposition in the corneal stroma, may occur.[4] Treatment of acute calcareous degeneration is an emergency. Inappropriate or delayed treatment will cause serious consequences and lead to the necessity of a corneal transplantation. Here, we report a rare case of acute calcareous degeneration caused by ocular GVHD. A medical device composed of amniotic membrane (ProKera® device, PD) successfully inhibited the deterioration of the disease when conventional treatments were ineffective.

  Case Report Top

A 27-year-old man suffered from ocular GVHD following HSCT for the treatment of T-cell acute lymphoblastic leukemia. At 11 months after HSCT, he complained of dryness, blurred vision, and photophobia in both eyes. Upon examination, his refractory error was –2.75 to 0.50 X 15 in the right eye and –1.50 to 0.50 X 5 in the left eye. His best-corrected visual acuity was 20/40 in his right eye and 20/30 in his left eye. Under slit-lamp biomicroscopy, bilateral corneal erosions with intrastromal deposition of calcium were found in both eyes [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. The patient was therefore diagnosed as having bilateral ocular GVHD-related keratopathy. Although topical artificial tears, corticosteroids, cyclosporin, and autologous serum were used immediately, his ocular condition progressed. Bilateral contact lens usage was then performed after 4 weeks, followed by bilateral punctal plug insertion after 8 weeks. However, the condition continued to deteriorate [Fig. 1e-h]. In vivo confocal microscopy revealed significant infiltrate of dendritic cells in both corneas and a decrease in corneal endothelial density in the right eye. Single or multi-layered amniotic membrane transplantation was suggested, but the patient rejected to receive surgery in the operative room. A medical device composed of self-retained cryopreserved amniotic membrane (ProKera, Bio-Tissue Inc, Miami, FL, United States) was applied in both eyes after 3 months. After application of the amniotic membrane, the corneal condition improved significantly. Repeated application of amniotic membrane (ProKera® device, PD) was performed. Three weeks later, the patient reported complete resolution of ocular discomfort in both eyes. Decreased inflammation and almost complete re-epithelialization of the cornea were documented [Fig. 1i-l]. The ocular surface was silent without significant corneal erosion during the following 6 months. The intracorneal calcium remained stable without progression.
Figure 1: (a-d) Corneal erosion and mild intrastromal deposition of calcium were found in both eyes. In the right eye, corneal Descemet membrane folding was found in the upper part. (e-h) With intensive topical eyedrop treatment, bilateral punctal occlusion, and bandage contact lens use for 1 month, the large corneal epithelial defects and areas of calcium deposition in the corneal stroma progressed. (i-l) After repeated insertion of sutureless, cryopreserved amniotic membrane twice over a sequential 5 weeks, the corneas almost completely re-epithelialized, and the surface inflammation decreased. However, the intrastromal calcium remained. The ocular surface condition has continued to remain stable

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  Discussion Top

Treatment of ocular GVHD has long been challenging. Topical lubricants, anti-inflammatory agents, punctal occlusion, therapeutic contact lens, and tarsorrhaphy have been suggested to be useful. However, these treatment options are palliative in nature and function by decreasing tear evaporation, improving lubrication, and decreasing blink-induced trauma to the ocular surface.[5] Blood preparations (such as autologous serum tears and platelet lysates) are well known to have anti-inflammatory, epitheliotrophic, and neurotrophic effects.[6],[7] However, the inconvenience of their preparation and the need for frequent application are their drawbacks. Amniotic membrane has been demonstrated to be effective in immune or non–immune-related dry eye disease,[8] severe chemical/thermal injury, and Stevens Johnson syndrome[9] because of its anti-inflammatory, anti-scarring, and regenerative properties. Such properties may be useful for the treatment of ocular GVHD.

In aggressive, chronic ocular GVHD, sutured amniotic membrane transplantation has been reported to accelerate corneal epithelialization and reduce inflammation.[10] However, to the best of our knowledge, there were no reports using a medical device composed of amniotic membrane to inhibit the rapid progression of acute calcareous degeneration caused by ocular GVHD. Traditional sutured amniotic membrane, no matter single or multiple layered, must be performed in the operating room, which is inconvenient for both doctors and patients. A medical device composed of sutureless cryopreserved amniotic membrane (ProKera® device, PD) is more advantageous as it can be easily administered in the office. In our patient, the corneal erosions, ocular surface inflammation, and acute calcareous degeneration progressed rapidly before the insertion of amniotic membrane (ProKera) despite intensive conventional treatment. The placement of amniotic membrane (ProKera) significantly improved the condition and prevented further deterioration. Initiating early amniotic membrane treatment in severe, acute, ocular GVHD-related keratopathy can be an effective anti-inflammatory treatment to restore corneal surface integrity, visual acuity, and avoid serious ocular complications. If such treatment can be performed early, acute calcareous degeneration can be prevented, and it can decrease the need for corneal transplantation to restore visual acuity.

  Conclusion Top

A medical device composed of amniotic membrane is an important tool for corneal surface disease because of its therapeutic effects and convenience of usage.

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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Nassar A, Tabbara KF, Aljurf M. Ocular manifestations of graft-versus-host disease. Saudi J Ophthalmol 2013;27:215-22.  Back to cited text no. 1
Nassiri N, Eslani M, Panahi N, Mehravaran S, Ziaei A, Djalilian AR. Ocular graft versus host disease following allogeneic stem cell transplantation: A review of current knowledge and recommendations. J Ophthalmic Vis Res 2013;8:351-8.  Back to cited text no. 2
  [Full text]  
Tabbara KF, Al-Ghamdi A, Al-Mohareb F, Ayas M, Chaudhri N, Al-Sharif F, et al. Ocular findings after allogeneic hematopoietic stem cell transplantation. Ophthalmology 2009;116:1624-9.  Back to cited text no. 3
Yen P-T, Hou Y-C, Lin W-C, Hu F-R. Recurrent corneal perforation and acute calcareous corneal degeneration in chronic graft-versus-host disease. J Formos Med Assoc 2006;105:334-9.  Back to cited text no. 4
Tung CI. Current approaches to treatment of ocular graft-versus-host disease. Int Ophthalmol Clin 2017;57:65-88.  Back to cited text no. 5
Huang C-J, Sun Y-C, Christopher K, Pai AS-I, Lu C-J, Hu F-R, et al. Comparison of corneal epitheliotrophic capacities among human platelet lysates and other blood derivatives. PLoS One 2017;12:e0171008.  Back to cited text no. 6
Chen Y-M, Hu F-R, Huang J-Y, Shen EP, Tsai T-Y, Chen W-L. The effect of topical autologous serum on graft re-epithelialization after penetrating keratoplasty. Am J Ophthalmol 2010;150:352-9.e2.  Back to cited text no. 7
Cheng AM, Zhao D, Chen R, Yin HY, Tighe S, Sheha H, et al. Accelerated restoration of ocular surface health in dry eye disease by self-retained cryopreserved amniotic membrane. Ocul Surf 2016;14:56-63.  Back to cited text no. 8
Liu J, Sheha H, Fu Y, Liang L, Tseng SC. Update on amniotic membrane transplantation. Expert Rev Ophthalmol 2010;5:645-61.  Back to cited text no. 9
Peric Z, Skegro I, Durakovic N, Desnica L, Pulanic D, Serventi-Seiwerth R, et al. Amniotic membrane transplantation—A new approach to crossing the HLA barriers in the treatment of refractory ocular graft-versus-host disease. Bone Marrow Transplant 2018;53:1466-9.  Back to cited text no. 10


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