CASE REPORT
Descemet Membrane Endothelial Keratoplasty in a Child With Corneal Endothelial Dysfunction in Kearns–Sayre Syndrome Johannes Gonnermann, MD,* Matthias K. J. Klamann, MD,* Anna-Karina B. Maier, MD,* Eckart Bertelmann, MD,* Jan Schroeter, MD,† Katja von Au, MD,‡ Antonia M. Joussen, MD,* and Necip Torun, MD*
Purpose: To evaluate clinical outcomes and complications after Descemet membrane endothelial keratoplasty (DMEK) in a child.
Methods: A 12-year-old boy with Kearns–Sayre syndrome (chronic progressive external ophthalmoplegia, cardiac conduction block, and pigmentary retinal degeneration) and corneal endothelial dysfunction was successfully treated with DMEK. Corneal transparency, central corneal thickness (CCT), endothelial cell density (ECD), visual outcomes, and complication rates were measured during the follow-up of 6 months. Results: Best spectacle-corrected visual acuity (BSCVA) improved
from counting fingers at 4 feet preoperatively to 20/100, 1 week after surgery. The ECD of the graft was 2595 cells per square millimeter. The CCT diminished from 837 mm preoperatively to 735 mm 1 week after surgery. Six months postoperatively, the BSCVA was still 20/ 100, and the cornea remained clear and compact. The ECD was 2341 cells per square millimeter and CCT was almost normal with 583 mm. No postoperative complications were observed. Fundus examination showed atypical pigmentary retinal degeneration with arterial narrowing. Electroretinography with full-field flash stimulation showed bilaterally severe retinal dysfunction with absent photopic and scotopic amplitudes explaining the reduced BSCVA.
Conclusions: Although DMEK has been used in adult populations, we are unaware of previous reports of DMEK in a child. DMEK should be considered as a feasible technique in pediatric patients with endothelial dysfunction. Key Words: Descemet membrane endothelial keratoplasty, Kearns– Sayre syndrome, endothelial dysfunction, children (Cornea 2014;33:1232–1234) Received for publication April 22, 2014; revision received July 21, 2014; accepted July 22, 2014. Published online ahead of print September 11, 2014. From the *Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Berlin, Germany; †Cornea Bank Berlin, University Tissue Bank, Charité— Universitätsmedizin Berlin, Berlin, Germany; and ‡Center for Social Pediatrics, Charité—Universitätsmedizin Berlin, Berlin, Germany. Supported by the Friedrich C. Luft Clinical Scientist Pilot Program funded by Volkswagen Foundation and Charité Foundation, Berlin, Germany (A.-K. B. M.). The other authors have no other funding or conflicts of interest to disclose. Reprints: Johannes Gonnermann, MD, Department of Ophthalmology, Charité— Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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E
ndothelial keratoplasty (EK) has become the leading surgical approach in the management of corneal endothelial disorders with the introduction of various techniques such as Descemet stripping (automated) endothelial keratoplasty and Descemet membrane endothelial keratoplasty (DMEK) in adults. 1,2 Because DMEK is performed through a small incision in a closed eye, it allows faster visual recovery, minimal refractive change, and better preservation of ocular structural integrity compared with conventional full-thickness penetrating keratoplasty or other EK techniques.1,2 Although these procedures have been used successfully in adult populations, we are unaware of previous reports of DMEK in a child.
CASE REPORT A 12-year-old boy with bilateral ptosis, bilateral hazy corneas, progressive visual problems, sensorineural hearing loss, and proximal muscle weakness of all 4 extremities was referred to our clinic in February 2011. At the age of 9 years, after suffering from circulatory collapse and seizures with vomiting every 6 to 8 weeks over 8 months, the patient had a syncopal episode followed by frothing, stupor, and bradycardia. A transvenous pacemaker had to be inserted in view of complete atrioventricular heart block. Previous magnetic resonance imaging showed abnormal hyperintense signals in both globi pallidi. On histopathologic examination, muscle biopsy showed mild atrophic changes and interspersed collagen and adipose tissue. Modified Gomori stain showed multiple “ragged red” fibers and COX-negative muscle fibers in his left outer thigh muscle. Genetic evaluation showed large-scale single deletion in the mitochondrial DNA in peripheral blood cells. On ocular examination, the best spectacle-corrected visual acuity (BSCVA) was 20/50 in both eyes. The boy had severe bilateral ptosis and chronic progressive external ophthalmoplegia with highly restricted range of eye movement in all directions of gaze (Fig. 1A). Slit-lamp examination showed epithelial and diffuse stromal edema as well as irregularity of the corneal endothelium but without guttae. In December 2012, corneal edema worsened with a central corneal thickness (CCT) of 837 mm in the right eye and 833 mm in the left eye with circular superficial limbal corneal vascularization (Fig. 1B). The BSCVA was counting fingers at 4 feet. After obtaining consent from the parents, he underwent DMEK in March 2013 on his right eye under general anesthesia. Cornea Volume 33, Number 11, November 2014
Cornea Volume 33, Number 11, November 2014
Outcomes and Complications After DMEK in a Child
FIGURE 1. Clinical images of a 12year-old boy with corneal endothelial dysfunction in KSS. A, Frontal portrait. B, Preoperative slit-lamp image showing a diffusely edematous cornea as the result of endothelial dysfunction with circular superficial limbal corneal vascularization. No stromal scarring is present. C, Slit-lamp image 6 months after DMEK showing a clear cornea with no signs of edema and resolved superficial limbal corneal vascularization under topical steroids. D, Postoperative fundus image of the right eye showing atypical pigmentary retinal degeneration with arterial narrowing.
SURGICAL TECHNIQUE Donor Preparation Stripping of the Descemet membrane (DM) from the donor corneal stroma was performed immediately before transplantation with the donor tissue submerged in balanced salt solution (BSS, Alcon, Inc, Fort Worth, TX). After gently scoring the peripheral DM with a blunt instrument, the corneoscleral rim was stained with 0.06% trypan blue (Vision Blue, DORC Deutschland GmbH, Berlin, Germany) for 60 seconds and was placed in a corneal viewing chamber containing corneal storage solution. The scored edges of DM then were grasped with non-toothed forceps and slowly stripped away from the stroma half way to the center. Central partial-thickness trephination then was performed with donor cornea endothelial side up on the punch block. The diameter of the graft was 8.5 mm. The separation of the central punched DM from the donor stroma was completed using 2 no toothed forceps. The stripped DM was stained with trypan blue, after it was placed back in the recess of the corneoscleral rim.
Recipient Preparation and Donor Insertion The pupil was constricted with acetylcholine chloride 0.01% (Miochol-E, Bausch & Lomb, Rochester, NY) after which 1 peripheral iridectomy was performed at the 7 o’clock position. Central descemetorhexis with a diameter of 9.0 mm was performed under BSS and trypan blue using a Descemet incision hook with irrigation by Althaus/Cartsburg (Geuder, Heidelberg, Germany), and the central portion of DM was removed from the eye. The trypan blue–stained donor Descemet roll was sucked into a semirigid nonstick tubing connected to a syringe filled with BSS. Short bursts of BSS were used to irrigate the DM gently into the anterior chamber. Ó 2014 Lippincott Williams & Wilkins
The graft was oriented endothelial side down (donor DM facing the recipient posterior stroma) onto the recipient posterior stroma by careful indirect manipulation of the tissue with air and fluid. The anterior chamber was completely filled with air for 30 to 45 minutes, followed by a sufficient air– liquid (2/3) exchange to pressurize the eye and to prevent pupillary block. Furthermore, after DMEK, the child was kept in a supine position for 24 hours. Postoperative topical treatment included a combination of steroid (prednisolone acetate 1%, 5 times daily), antibiotic (ofloxacin, 5 times daily), and lubricant eye drops (5 times daily). One week after surgery, the BSCVA improved to 20/ 100 in the right eye. The endothelial cell density of the graft was 2595 cells per square millimeter. The CCT diminished to 735 mm. Six months postoperatively, the BSCVA was still 20/100, and the cornea remained clear and compact. The endothelial cell density was 2341 cells per square millimeter, and CCT was almost normal with 583 mm (Fig. 1B). Circular superficial limbal corneal vascularization disappeared under topical steroids without ghost vessels. No other postoperative complications were observed. Fundus examination showed atypical pigmentary retinal degeneration with arterial narrowing (Fig. 1C). Electroretinography with full-field flash stimulation showed bilaterally severe retinal dysfunction with absent photopic and scotopic amplitudes explaining the reduced BSCVA.
DISCUSSION Kearns–Sayre syndrome (KSS) is a rare mitochondrial cytopathy, first described in a case report of 2 patients by Kearns and Sayre3 in 1958 and characterized by a triad consisting of chronic progressive external ophthalmoplegia, complete cardiac block, and bilateral pigmentary retinal www.corneajrnl.com |
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degeneration. Few reports have been published concerning corneal changes in mitochondrial cytopathy. In 1989, Ohkoshi et al4 first reported corneal endothelial dystrophy in a case of KSS, where the mean cell size of the corneal endothelium was 5 times as large as normal, the mean cell density was decreased, and severe pleomorphism and polymegathism were prominent in specular microscopy. They assumed that the corneal endothelial abnormality might be the result of mitochondrial enzyme deficiency of the corneal endothelial cell pump. Histopathologically, corneal endothelial cells contain a large number of mitochondria and might be one of the tissues vulnerable to mitochondrial dysfunction. In our case, because of severe corneal endothelial dysfunction in KSS, DMEK was performed. The traditional treatment for endothelial decompensation is penetrating keratoplasty, but has a high incidence of graft failure, between 50% and 60%.5 Few data on the outcome of other EK procedures such as Descemet stripping (automated) endothelial keratoplasty in children exisit.6 But they demonstrate the advantages of EK over full-thickness penetrating keratoplasty, including lower graft rejection rate, increased wound stability, and faster visual recovery without inducing significant astigmatism.
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| www.corneajrnl.com
Cornea Volume 33, Number 11, November 2014
However, new forms of complications such as graft dislocation, pupillary block, and primary graft failure are accompanied with EK. Our patient demonstrated good improvement of visual acuity without any sign of graft detachment or failure at the last follow-up visit. DMEK should be considered as a feasible technique in pediatric patients with endothelial dysfunction. REFERENCES 1. Guerra FP, Anshu A, Price MO, et al. Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival and endothelial cell loss. Ophthalmology. 2011;118:2368–2373. 2. Tan DT, Dart JK, Holland EJ, et al. Corneal transplantation. Lancet. 2012; 379:1749–1761. 3. Kearns TP, Sayre GP. Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases. Arch Ophthalmol. 1958;60:280–289. 4. Ohkoshi K, Ishida N, Yamaguchi T, et al. Corneal endothelium in a case of mitochondrial encephalomyopathy (Kearns-Sayre Syndrome). Cornea. 1989;8:210–214. 5. Al-Ghamdi A, Al-Rajhi A, Wagoner MD. Primary pediatric keratoplasty: indications, graft survival, and visual outcome. J AAPOS. 2007;11:41–47. 6. Fernandez MM, Buckley EG, Afshari NA. Descemet stripping automated endothelial keratoplasty in a child. J AAPOS. 2008;12:314–316.
Ó 2014 Lippincott Williams & Wilkins
Descemet Membrane Endothelial Keratoplasty in a Child With Corneal Endothelial Dysfunction in Kearns–Sayre Syndrome Johannes Gonnermann, MD,* Matthias K. J. Klamann, MD,* Anna-Karina B. Maier, MD,* Eckart Bertelmann, MD,* Jan Schroeter, MD,† Katja von Au, MD,‡ Antonia M. Joussen, MD,* and Necip Torun, MD*
Purpose: To evaluate clinical outcomes and complications after Descemet membrane endothelial keratoplasty (DMEK) in a child.
Methods: A 12-year-old boy with Kearns–Sayre syndrome (chronic progressive external ophthalmoplegia, cardiac conduction block, and pigmentary retinal degeneration) and corneal endothelial dysfunction was successfully treated with DMEK. Corneal transparency, central corneal thickness (CCT), endothelial cell density (ECD), visual outcomes, and complication rates were measured during the follow-up of 6 months. Results: Best spectacle-corrected visual acuity (BSCVA) improved
from counting fingers at 4 feet preoperatively to 20/100, 1 week after surgery. The ECD of the graft was 2595 cells per square millimeter. The CCT diminished from 837 mm preoperatively to 735 mm 1 week after surgery. Six months postoperatively, the BSCVA was still 20/ 100, and the cornea remained clear and compact. The ECD was 2341 cells per square millimeter and CCT was almost normal with 583 mm. No postoperative complications were observed. Fundus examination showed atypical pigmentary retinal degeneration with arterial narrowing. Electroretinography with full-field flash stimulation showed bilaterally severe retinal dysfunction with absent photopic and scotopic amplitudes explaining the reduced BSCVA.
Conclusions: Although DMEK has been used in adult populations, we are unaware of previous reports of DMEK in a child. DMEK should be considered as a feasible technique in pediatric patients with endothelial dysfunction. Key Words: Descemet membrane endothelial keratoplasty, Kearns– Sayre syndrome, endothelial dysfunction, children (Cornea 2014;33:1232–1234) Received for publication April 22, 2014; revision received July 21, 2014; accepted July 22, 2014. Published online ahead of print September 11, 2014. From the *Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Berlin, Germany; †Cornea Bank Berlin, University Tissue Bank, Charité— Universitätsmedizin Berlin, Berlin, Germany; and ‡Center for Social Pediatrics, Charité—Universitätsmedizin Berlin, Berlin, Germany. Supported by the Friedrich C. Luft Clinical Scientist Pilot Program funded by Volkswagen Foundation and Charité Foundation, Berlin, Germany (A.-K. B. M.). The other authors have no other funding or conflicts of interest to disclose. Reprints: Johannes Gonnermann, MD, Department of Ophthalmology, Charité— Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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E
ndothelial keratoplasty (EK) has become the leading surgical approach in the management of corneal endothelial disorders with the introduction of various techniques such as Descemet stripping (automated) endothelial keratoplasty and Descemet membrane endothelial keratoplasty (DMEK) in adults. 1,2 Because DMEK is performed through a small incision in a closed eye, it allows faster visual recovery, minimal refractive change, and better preservation of ocular structural integrity compared with conventional full-thickness penetrating keratoplasty or other EK techniques.1,2 Although these procedures have been used successfully in adult populations, we are unaware of previous reports of DMEK in a child.
CASE REPORT A 12-year-old boy with bilateral ptosis, bilateral hazy corneas, progressive visual problems, sensorineural hearing loss, and proximal muscle weakness of all 4 extremities was referred to our clinic in February 2011. At the age of 9 years, after suffering from circulatory collapse and seizures with vomiting every 6 to 8 weeks over 8 months, the patient had a syncopal episode followed by frothing, stupor, and bradycardia. A transvenous pacemaker had to be inserted in view of complete atrioventricular heart block. Previous magnetic resonance imaging showed abnormal hyperintense signals in both globi pallidi. On histopathologic examination, muscle biopsy showed mild atrophic changes and interspersed collagen and adipose tissue. Modified Gomori stain showed multiple “ragged red” fibers and COX-negative muscle fibers in his left outer thigh muscle. Genetic evaluation showed large-scale single deletion in the mitochondrial DNA in peripheral blood cells. On ocular examination, the best spectacle-corrected visual acuity (BSCVA) was 20/50 in both eyes. The boy had severe bilateral ptosis and chronic progressive external ophthalmoplegia with highly restricted range of eye movement in all directions of gaze (Fig. 1A). Slit-lamp examination showed epithelial and diffuse stromal edema as well as irregularity of the corneal endothelium but without guttae. In December 2012, corneal edema worsened with a central corneal thickness (CCT) of 837 mm in the right eye and 833 mm in the left eye with circular superficial limbal corneal vascularization (Fig. 1B). The BSCVA was counting fingers at 4 feet. After obtaining consent from the parents, he underwent DMEK in March 2013 on his right eye under general anesthesia. Cornea Volume 33, Number 11, November 2014
Cornea Volume 33, Number 11, November 2014
Outcomes and Complications After DMEK in a Child
FIGURE 1. Clinical images of a 12year-old boy with corneal endothelial dysfunction in KSS. A, Frontal portrait. B, Preoperative slit-lamp image showing a diffusely edematous cornea as the result of endothelial dysfunction with circular superficial limbal corneal vascularization. No stromal scarring is present. C, Slit-lamp image 6 months after DMEK showing a clear cornea with no signs of edema and resolved superficial limbal corneal vascularization under topical steroids. D, Postoperative fundus image of the right eye showing atypical pigmentary retinal degeneration with arterial narrowing.
SURGICAL TECHNIQUE Donor Preparation Stripping of the Descemet membrane (DM) from the donor corneal stroma was performed immediately before transplantation with the donor tissue submerged in balanced salt solution (BSS, Alcon, Inc, Fort Worth, TX). After gently scoring the peripheral DM with a blunt instrument, the corneoscleral rim was stained with 0.06% trypan blue (Vision Blue, DORC Deutschland GmbH, Berlin, Germany) for 60 seconds and was placed in a corneal viewing chamber containing corneal storage solution. The scored edges of DM then were grasped with non-toothed forceps and slowly stripped away from the stroma half way to the center. Central partial-thickness trephination then was performed with donor cornea endothelial side up on the punch block. The diameter of the graft was 8.5 mm. The separation of the central punched DM from the donor stroma was completed using 2 no toothed forceps. The stripped DM was stained with trypan blue, after it was placed back in the recess of the corneoscleral rim.
Recipient Preparation and Donor Insertion The pupil was constricted with acetylcholine chloride 0.01% (Miochol-E, Bausch & Lomb, Rochester, NY) after which 1 peripheral iridectomy was performed at the 7 o’clock position. Central descemetorhexis with a diameter of 9.0 mm was performed under BSS and trypan blue using a Descemet incision hook with irrigation by Althaus/Cartsburg (Geuder, Heidelberg, Germany), and the central portion of DM was removed from the eye. The trypan blue–stained donor Descemet roll was sucked into a semirigid nonstick tubing connected to a syringe filled with BSS. Short bursts of BSS were used to irrigate the DM gently into the anterior chamber. Ó 2014 Lippincott Williams & Wilkins
The graft was oriented endothelial side down (donor DM facing the recipient posterior stroma) onto the recipient posterior stroma by careful indirect manipulation of the tissue with air and fluid. The anterior chamber was completely filled with air for 30 to 45 minutes, followed by a sufficient air– liquid (2/3) exchange to pressurize the eye and to prevent pupillary block. Furthermore, after DMEK, the child was kept in a supine position for 24 hours. Postoperative topical treatment included a combination of steroid (prednisolone acetate 1%, 5 times daily), antibiotic (ofloxacin, 5 times daily), and lubricant eye drops (5 times daily). One week after surgery, the BSCVA improved to 20/ 100 in the right eye. The endothelial cell density of the graft was 2595 cells per square millimeter. The CCT diminished to 735 mm. Six months postoperatively, the BSCVA was still 20/100, and the cornea remained clear and compact. The endothelial cell density was 2341 cells per square millimeter, and CCT was almost normal with 583 mm (Fig. 1B). Circular superficial limbal corneal vascularization disappeared under topical steroids without ghost vessels. No other postoperative complications were observed. Fundus examination showed atypical pigmentary retinal degeneration with arterial narrowing (Fig. 1C). Electroretinography with full-field flash stimulation showed bilaterally severe retinal dysfunction with absent photopic and scotopic amplitudes explaining the reduced BSCVA.
DISCUSSION Kearns–Sayre syndrome (KSS) is a rare mitochondrial cytopathy, first described in a case report of 2 patients by Kearns and Sayre3 in 1958 and characterized by a triad consisting of chronic progressive external ophthalmoplegia, complete cardiac block, and bilateral pigmentary retinal www.corneajrnl.com |
1233
Gonnermann et al
degeneration. Few reports have been published concerning corneal changes in mitochondrial cytopathy. In 1989, Ohkoshi et al4 first reported corneal endothelial dystrophy in a case of KSS, where the mean cell size of the corneal endothelium was 5 times as large as normal, the mean cell density was decreased, and severe pleomorphism and polymegathism were prominent in specular microscopy. They assumed that the corneal endothelial abnormality might be the result of mitochondrial enzyme deficiency of the corneal endothelial cell pump. Histopathologically, corneal endothelial cells contain a large number of mitochondria and might be one of the tissues vulnerable to mitochondrial dysfunction. In our case, because of severe corneal endothelial dysfunction in KSS, DMEK was performed. The traditional treatment for endothelial decompensation is penetrating keratoplasty, but has a high incidence of graft failure, between 50% and 60%.5 Few data on the outcome of other EK procedures such as Descemet stripping (automated) endothelial keratoplasty in children exisit.6 But they demonstrate the advantages of EK over full-thickness penetrating keratoplasty, including lower graft rejection rate, increased wound stability, and faster visual recovery without inducing significant astigmatism.
1234
| www.corneajrnl.com
Cornea Volume 33, Number 11, November 2014
However, new forms of complications such as graft dislocation, pupillary block, and primary graft failure are accompanied with EK. Our patient demonstrated good improvement of visual acuity without any sign of graft detachment or failure at the last follow-up visit. DMEK should be considered as a feasible technique in pediatric patients with endothelial dysfunction. REFERENCES 1. Guerra FP, Anshu A, Price MO, et al. Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival and endothelial cell loss. Ophthalmology. 2011;118:2368–2373. 2. Tan DT, Dart JK, Holland EJ, et al. Corneal transplantation. Lancet. 2012; 379:1749–1761. 3. Kearns TP, Sayre GP. Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases. Arch Ophthalmol. 1958;60:280–289. 4. Ohkoshi K, Ishida N, Yamaguchi T, et al. Corneal endothelium in a case of mitochondrial encephalomyopathy (Kearns-Sayre Syndrome). Cornea. 1989;8:210–214. 5. Al-Ghamdi A, Al-Rajhi A, Wagoner MD. Primary pediatric keratoplasty: indications, graft survival, and visual outcome. J AAPOS. 2007;11:41–47. 6. Fernandez MM, Buckley EG, Afshari NA. Descemet stripping automated endothelial keratoplasty in a child. J AAPOS. 2008;12:314–316.
Ó 2014 Lippincott Williams & Wilkins
