CLINICAL SCIENCE
Keratoplasty in Patients With Intellectual Disability Barbara Koller, MD, Thomas F. Neuhann, MD, and Irmingard M. Neuhann, MD
Purpose: The aim was to report the outcome of keratoplasty in patients with intellectual disability (ID).
Methods: All patients with ID who had undergone keratoplasty at the Eye Department, Red Cross Hospital, Munich, between January 1, 1991, and December 31, 2010, were identified and recalled for examination. In cases of missing data, the information contained in the patient’s chart was analyzed and/or his ophthalmologist was contacted.
Results: A total of 38 eyes (29 patients) that had undergone 53 keratoplasty procedures were included in the analysis. In 20 patients, the general diagnosis was Down syndrome, 1 patient had ID as a result of brain tumor excision, and 8 patients had ID of an unknown origin. The indication for the primary keratoplasty (n = 35) was keratoconus in 33 patients and corneal opacity because of exposure in facial nerve palsy in 2 patients. In the 3 remaining patients, the first procedure at the study institution was a repeat keratoplasty. The median follow-up was 9 years (minimum 6 months, maximum 20 years). The graft survival rate of the primary graft was 86% (n = 30/35) from 27 months to 11 years. At the last follow-up visit, a clear graft was present in 89% of all the patients (n = 34/38). One eye underwent enucleation, and 3 other eyes remained with a cloudy graft after multiple interventions for rejection/corneal ulceration.
Conclusions: The majority of the patients with ID clearly benefited from keratoplasty, although a few deleterious courses occurred. Keratoplasty in these individuals can be considered whenever patients can no longer comply with the visual demands of their particular individual life. Key Words: Down syndrome, intellectual disability, keratoplasty, graft rejection (Cornea 2014;33:10–13)
P
enetrating keratoplasty (PKP) is a surgical procedure with a high success rate, especially for noninflammatory indications such as corneal ectasia, in which 5-year graft survival rates of 90% to 98% are reported.1–6 Besides the indication for surgery, graft survival is also highly dependent on other factors, such as surgical technique, concomitant diseases, and quality and intensity of short- and long-term follow-up care.1–8
Received for publication April 18, 2013; revision received August 28, 2013; accepted August 29, 2013. Published online ahead of print October 31, 2013. From the Eye Department, Red Cross Hospital, Munich, Germany. The authors have no funding or conflicts of interest to disclose. Reprints: Barbara Koller, Eye Department, Red Cross Hospital, Helene-WeberAllee 19, 80637 München, Germany (e-mail: [email protected]). Copyright © 2013 by Lippincott Williams & Wilkins
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Visually impairing corneal disease requiring corneal grafting may be associated with syndromes that go along with intellectual disability (ID), such as the Down syndrome.2,9,10 Especially in this patient subgroup, concomitant diseases with negative impact (eg, atopic dermatitis) or behavioral issues (such as aggressive eye rubbing) have been reported to reduce the long-term graft survival.2,8,9,11,12 However, optical rehabilitation is important for quality of life, especially in reduced mental function.13–15 The prognosis of corneal procedures in this patient population has been evaluated in only a few reports, and all of them include surgical procedures dating back to the 1970s and 1980s, and only single reports include cases operated on from the year 2000 onward.2,8,9,12,15,16 The purpose of this study was to analyze the outcome of all keratoplasty procedures in patients with ID, who had been treated at our institution over the past 20 years, in which we used the same surgical standard.
PATIENTS AND METHODS Patients All patients with ID who had undergone a keratoplasty procedure between January 1, 1991, and December 31, 2010, at the Eye Department, Red Cross Hospital, Munich, were identified retrospectively through the computerized database of the institution (Informed X.9.8; Informed GmbH, EfringenKirchen, Germany). For this, all patients who underwent a keratoplasty procedure performed under general anesthesia were considered to be eligible. The charts of all identified patients were checked manually for evidence of ID mainly by identifying the diagnosis of Down syndrome and/or evidence of a legal guardian, together with the legal status of being “mentally handicapped” (obvious from a state disability identification card entitling them to public support and benefits for participation in community life). All the eligible patients were not able to lead an independent life, living either in an institution (n = 9) or with their families (n = 20). According to the criteria of the World Health Organization, all the patients were moderately to severely handicapped.17 From these cases, the following data were transferred into an Excel sheet: name, first name, date of birth, date of surgery, ophthalmological history, general history, intraoperative and postoperative complications, additional surgical interventions, and the date of the last visit. All the patients were then invited for a follow-up visit by phone. Whenever this was not possible, the available information was retrieved from the patient’s chart or the treating ophthalmologist. Cornea Volume 33, Number 1, January 2014
Cornea Volume 33, Number 1, January 2014
Surgical Technique Transplants were prepared either with a manual trephine (diameter $8.5 mm, Neuhann trephine; Geuder AG, Heidelberg, Germany) or with the guided trephine system (Krumeich GTS, diameter 7.5–8.5 mm; Polytech Ophthalmologie GmbH, Robdorf, Germany). After trephination of the recipient with either a motor trephine (diameter $8.5 mm, Neuhann trephine; Geuder AG) or the Krumeich GTS, the graft was fixated with 16 single sutures or 2 running double nontorque sutures (10-0 Nylon). All the patients were referred back to their ophthalmologist after the procedure was performed and were only seen for suture removal after 12 and 15 months and in cases of any postoperative problems. The postoperative standard medication consisted of dexamethasone phosphate given 4 times a day tapered over 6 months and artificial tears applied 4 times a day. After 6 months, local steroids were discontinued unless an episode of rejection occurred. In the case of a rejection, the frequency of applying topical steroids was increased to an hourly interval and/or betamethasone was administered subconjunctivally. In cases of a repeat keratoplasty after a rejection, oral immunosuppressive therapy was administered, consisting of either oral prednisolone (starting at 1 mg/kg) tapered typically over 6 months and/or oral mycophenolate mofetil (1 g twice daily) for 2 years, adjusted according to tolerance and clinical findings.
RESULTS During the study period, a total of 55 keratoplasty procedures on 40 eyes of 31 patients were performed. A total of 19 patients presented to the study institution for a followup examination upon invitation. Three patients had already died, and 9 patients were unable to present themselves because of failure to contact or because of uncooperative caregivers. These patients were included with the findings recorded in the chart from their last examination. Two cases were lost to any form of follow-up and were excluded from further analysis, leaving 38 eyes from 29 patients with 53 keratoplasty procedures for the final analysis. The median age at the time of the first keratoplasty procedure was 38 years (minimum 13, maximum 55). The median follow-up was for 9 years (minimum 6 months, maximum 20 years). A total of 31 eyes (82%) of 24 patients were followed up for .5 years and 18 eyes (47%) of 13 patients were followed up for .10 years.
Diagnosis In 20 patients, the general diagnosis was Down syndrome, 1 patient had an ID caused by brain tumor excision at the age of 13 years, and 8 patients had an ID of an unknown origin. The indication for the first PKP (n = 35) was keratoconus in 33 patients and corneal opacity caused by exposure in facial nerve palsy in 2 patients. A total of 13 keratoplasty procedures were performed on an emergency basis: spontaneous perforation in 1 patient, and acute hydrops (surgery within 3 weeks of the first presentation) in 12 patients. The reasons for the 18 repeat keratoplasty procedures (n = 8 eyes) were nonimmunological graft decompensation in Ó 2013 Lippincott Williams & Wilkins
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3 eyes (5, 6, and 11 years after the initial PKP), decompensation after graft rejection in 11 cases, therapy-resistant corneal melt because of a persistent ocular surface defect in 2 patients, and acute rejection with ulcer in 2 patients.
Prior Surgical Interventions In the 29 study patients, 6 eyes had undergone a PKP procedure elsewhere. In 3 of these eyes, a repeat keratoplasty for graft decompensation (2 cases after graft rejection) was performed as the first procedure at the study institution. These cases were considered as repeat keratoplasties for analysis.
Surgical Details
All, except 2 eyes, were phakic at the time of the first intervention. Five eyes underwent a triple procedure (crystalline lens extraction, intraocular lens implantation, and PKP). In the 2 eyes with facial nerve palsy, a permanent tarsorrhaphy was performed simultaneously. In 1 eye, a Descemet stripping endothelial keratoplasty was performed for graft decompensation, 11 years after the original PKP. All other procedures were PKPs.
Complications In the 53 keratoplasty procedures, there was 1 intraoperative complication recorded, that is, injury of the anterior lens capsule during trephination in 1 case of repeat keratoplasty in the case with corneal melt. Postoperative complications included secondary glaucoma in 5 eyes and at least 1 episode of graft rejection in 8 eyes (including 2 eyes with a history of bacterial corneal ulcer). One of the cases with facial nerve palsy was only seen for 6 months and had persistent epithelial defects. A total of 6% of the primary keratoplasties (n = 2/35) and 11% of all the cases (n = 4/38) were considered final “failures” (see below). The second case with facial nerve palsy developed a corneal ulcer with purulent endophthalmitis, which presented late, could not be managed conservatively, and underwent primary enucleation. Three other eyes (3 patients) with a history of rejection episodes/corneal ulcer underwent several repeat surgical procedures and remained with a failed graft because of graft rejection to date (see below).
Graft Survival Graft survival was defined as clear graft, failure as opacification, regardless of cause, and thus incompatible with useful vision, final failure referring to the status at the last follow-up visit. The graft survival rate of the primary graft (excluding the 3 cases of repeat keratoplasty as the first procedure at the study institution) was 89% (n = 31/35) up to 27 months and 86% (n = 30/35) thereafter up to 11 years (Fig. 1). At the last follow-up visit, a clear graft was present in 89% of all the cases (n = 34/38).
Functional Results In those eyes with complete preoperative and postoperative visual acuity recordings (n = 21), the median www.corneajrnl.com |
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FIGURE 1. Graph showing the Kaplan–Meier analysis of graft survival. Group 1: Survival of the primary graft transplanted in the study institution (n = 35). Group 2: Overall graft clarity of the same initial primary grafts (n = 35) at the last visit including regrafts (n = 10 in 5 eyes).
preoperative best-corrected visual acuity was 1.2 logarithm of the minimum angle of resolution (LogMAR; minimum 0.4, maximum 3). At the last follow-up visit, it had improved to a median of 0.7 LogMAR (minimum 0.2, maximum 3). Corneal topography at the last follow-up was available for 19 eyes (Pentacam; Oculus Optikgeräte, Wetzlar, Germany). The median topographic astigmatism was 2.9 diopters (minimum 0.4, maximum 10.6).
Further Surgical Procedures During the follow-up period in the 38 study eyes, 7 cataract surgeries were performed, including 1 case of simultaneous toric add-on intraocular lens implantation. One eye underwent a trabeculotomy and subsequent Ahmed Valve implantation for secondary glaucoma. One eye was enucleated (see above). A total of 31 eyes (including 1 repeat PKP as the first procedure in our institute) had no further corneal interventions after the first PKP procedure, 1 eye underwent a second PKP, and 1 eye underwent Descemet stripping endothelial keratoplasty (see above). Five other eyes (5 patients) underwent .2 PKP. Three eyes underwent a total of 3 PKP because of graft rejection and/or corneal ulcer. The remaining 2 eyes underwent a total of 4 and 5 penetrating keratoplasties, because of graft rejection and/or corneal ulcer.
DISCUSSION Several studies have shown that corneal diseases, especially keratoconus, frequently occur in patients with ID.9–11 The prevalence of keratoconus in this patient group has been estimated to be between 2.3% and 7.5%,10,11 the prevalence in patients with the Down syndrome being even higher (3%–20%).8,9,11,18 Whether genetic alterations leading to structural and biochemical changes of the cornea or external
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factors, such as extensive eye rubbing, are responsible for this, or a combination of both, is unclear.11 Optical rehabilitation must be considered especially important in patients with ID to ensure physical and mental well-being and optimize self-dependence.15 Even though in our study we did not evaluate the level of visual acuity required for this, our impression was that patients who had a visual acuity of $0.3 (#0.5 LogMAR) uniformly got along well in daily life, often denying further optical aids to improve this vision level. The results of our study demonstrate that the majority of the patients with ID will benefit from corneal grafting, which is contrary to the commonly encountered opinion that these patients do poorly.2 The median visual acuity (representing the majority of patients) improved after the surgical procedure. Even though the values of visual acuity are clearly below the levels in standard cases of keratoplasty for ectatic corneal disease with comparable surgical technique,5,6,16,19 one must consider the differing initial situation (eg, advanced pathology) and possible cooperation deficits in refraction/ visual acuity testing. The latter may be corroborated by the fact, that the mean postoperative topographic cylinder (2.9 diopters) was comparable or lower than in comparable standard keratoplasty cases.5,6,18 Considering only the primary grafts, the survival in this series was 86% from 2 years up to .11 years. These results compare favorably with 2 other recent series in patients with ID by García, García and Martínez8 (82.14% clear graft at the last visit) and Wroblewski et al15 (83% clear graft after 3 years). However, there are also a number of earlier series that reported lower success rates.2,12,16 Reasons for the overall poorer outcome, as compared with standard keratoplasty procedures (5-year survival in corneal ectatic disease, 90%–98%),1–6 have been proposed to be a high number of interventions on an emergency basis and/or the presence of concomitant problems such as lid anomalies, advanced findings such as hydrops, corneal infections, and (self-inflicted) trauma.2,6,9,12,15,16 This corresponds to our series, including 2 cases of facial nerve palsy and 12 cases with acute hydrops. The latter had severe discomfort and did not feel/were not considered by their caregivers capable to await resolution of the edema, which is generally the preferred approach.6,8 In none of these cases, however, did a final failure occur. These concomitant problems may also explain the relatively high rejection rate in our study (21%), which is higher than that reported for comparable standard keratoplasty cases.3,5,6,18 Because ID often causes a lack of communication, which may lead to a delay in timely awareness and diagnosis of complications, this condition may even be underreported.2,9,15 In this context, the quality of the postoperative care has been reported to play an important role in the long-term outcome.2,8,15 Superior academic training of the caregivers and patients with postoperative care at home has been reported to do better in the study by García, García and Martínez.8 In our study, we did not evaluate the level of quality of the postoperative care, which may also be difficult to assess in a standardized way. Therefore, from our study we cannot draw conclusions whether (and which) postoperative factors were associated with a reduced outcome, even though this Ó 2013 Lippincott Williams & Wilkins
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seems likely. From our impression, however, the individual diligence of the caregivers, which can be positively influenced by training as shown by García, García and Martínez8 rather than the level of their academic degree, has an influence on the outcome. In our study, there is no indirect evidence of a relation of intelligence level of patients and outcome, because only 2 out of the 4 final failures in our series occurred in patients who were disabled to a level where refraction or visual acuity testing was not possible. Other authors have found a relation between a lower intelligence level and reduced outcome, however, without the ability to distinguish whether the intelligence level or associated behavioral issues account for this.8,12 Actually, conclusions on the impact of ID itself, associated ocular pathologies (including genetic tissue alterations), or behavioral issues on the outcome/number and kind of complications can only be drawn in the presence of a matched control group (of normal intellect). This, however, is particularly difficult, because of the small overall number of patients with ID in combination with a high percentage of advanced pathology in these cases. Haugen et al12 proposed epikeratophakia as a surgical option for corneal disease in ID, because of the low complication rate with this procedure, leaving PKP only for patients with a higher intellectual status. Because we have, for a variety of reasons, never used epikeratophakia for the surgical treatment of keratoconus, we cannot contribute to this discussion. Because of the advances in deep anterior lamellar grafting techniques,20 this technique is no longer used to a noteworthy extent. The new lamellar corneal transplant techniques and their further development contain great promise to improve the overall prognosis in the patient subgroup with ID. In conclusion, it is to be noted that the long-term graft survival after a PKP in patients with ID is lower than in comparable standard PKP-operated patients.1–6,16 The majority of patients with ID, however, eventually retain a long-term clear graft and will achieve an increase in visual acuity. Keratoplasty in these individuals can be considered whenever patients can no longer comply with the visual demands of their particular individual life. The further development of lamellar grafting techniques may improve the overall outcome also in this patient group. The exact influence of associated factors on the outcome, such as the initial situation (eg, hydrops) and postoperative parameters (eg, eye rubbing, caregivers’ diligence) can reliably only be assessed in a prospective study with clearly defined and standardized outcome measures.
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ACKNOWLEDGMENTS The authors thank Dr. Marco Bornhauser, FEBO, for critical revision of this article. REFERENCES 1. Fasolo A, Capuzzo C, Fornea M, et al. Risk factors for graft failure after penetrating keratoplasty: 5-year follow-up from the corneal transplant epidemiological study. Cornea. 2011;30:1328–1335. 2. Völker-Dieben HJ, Odenthal MT, D’Amaro J, et al. Surgical treatment of corneal pathology in patients with Down’s syndrome. J Intellect Disabil Res. 1993;37:169–175. 3. Thompson RW Jr, Price MO, Bowers PJ, et al. Long-term graft survival after penetrating keratoplasty. Ophthalmology. 2003;110:1396–1402. 4. Borderie VM, Boëlle PY, Touzeau O, et al. Predicted long-term outcome of corneal transplantation. Ophthalmology. 2009;116:2354–2360. 5. Zhang YM, Wu SQ, Yao YF. Long-term comparison of full-bed deep anterior lamellar keratoplasty and penetrating keratoplasty in treating keratoconus. J Zhejiang Univ Sci B. 2013;14:438–450. 6. Basu S, Reddy JC, Vaddavalli PK, et al. Long-term outcomes of penetrating keratoplasty for keratoconus with resolved corneal hydrops. Cornea. 2012;31:615–620. 7. Reinhard T, Möller M, Sundmacher R. Penetrating keratoplasty in patients with atopic dermatitis with and without systemic cyclosporin A. Cornea. 1999;18:645–651. 8. García García GP, Martínez JB. Outcomes of penetrating keratoplasty in mentally retarded patients with keratoconus. Cornea. 2008;27:980–987. 9. McElvanney AM, Adhikary HP. Penetrating keratoplasty in the mentally retarded. Eye (Lond). 1997;11:786–789. 10. van Splunder J, Stilma JS, Bernsen RM, et al. Prevalence of ocular diagnoses found on screening 1539 adults with intellectual disabilities. Ophthalmology. 2004;111:1457–1463. 11. Haugen OH. Keratoconus in the mentally retarded. Acta Ophthalmol (Copenh). 1992;70:111–114. 12. Haugen OH, Høvding G, Eide GE, et al. Corneal grafting for keratoconus in mentally retarded patients. Acta Ophthalmol Scand. 2001;79:609–615. 13. Küchle M, Naumann GO. Penetrating keratoplasty for keratoconus in trisomy 21 [in German]. Klin Monbl Augenheilkd. 1992;200:228–230. 14. Isralowitz R, Madar M, Lifshitz T, et al. Visual problems among people with mental retardation. Int J Rehabil Res. 2003;26:149–152. 15. Wroblewski KJ, Mader TH, Torres MF, et al. Long-term graft survival in patients with Down syndrome after penetrating keratoplasty. Cornea. 2006;25:1026–1028. 16. Bodenmueller M, Goldblum D, Frueh BE. Penetrating keratoplasty in Down’s syndrome [in German]. Klin Monbl Augenheilkd. 2003;220: 99–102. 17. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva, Switzerland: World Health Organization; 1992. 18. Gaynon MW, Schimek RA. Down’s syndrome: a ten-year group study. Ann Ophthalmol. 1977;9:1493–1497. 19. Ruhswurm I, Scholz U, Pfleger T, et al. Three-year clinical outcome after penetrating keratoplasty for keratoconus with the guided trephine system. Am J Ophthalmol. 1999;127:666–673. 20. Sarnicola V, Toro P, Sarnicola C, et al. Long-term graft survival in deep anterior lamellar keratoplasty. Cornea. 2012;31:621–626.
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Keratoplasty in Patients With Intellectual Disability Barbara Koller, MD, Thomas F. Neuhann, MD, and Irmingard M. Neuhann, MD
Purpose: The aim was to report the outcome of keratoplasty in patients with intellectual disability (ID).
Methods: All patients with ID who had undergone keratoplasty at the Eye Department, Red Cross Hospital, Munich, between January 1, 1991, and December 31, 2010, were identified and recalled for examination. In cases of missing data, the information contained in the patient’s chart was analyzed and/or his ophthalmologist was contacted.
Results: A total of 38 eyes (29 patients) that had undergone 53 keratoplasty procedures were included in the analysis. In 20 patients, the general diagnosis was Down syndrome, 1 patient had ID as a result of brain tumor excision, and 8 patients had ID of an unknown origin. The indication for the primary keratoplasty (n = 35) was keratoconus in 33 patients and corneal opacity because of exposure in facial nerve palsy in 2 patients. In the 3 remaining patients, the first procedure at the study institution was a repeat keratoplasty. The median follow-up was 9 years (minimum 6 months, maximum 20 years). The graft survival rate of the primary graft was 86% (n = 30/35) from 27 months to 11 years. At the last follow-up visit, a clear graft was present in 89% of all the patients (n = 34/38). One eye underwent enucleation, and 3 other eyes remained with a cloudy graft after multiple interventions for rejection/corneal ulceration.
Conclusions: The majority of the patients with ID clearly benefited from keratoplasty, although a few deleterious courses occurred. Keratoplasty in these individuals can be considered whenever patients can no longer comply with the visual demands of their particular individual life. Key Words: Down syndrome, intellectual disability, keratoplasty, graft rejection (Cornea 2014;33:10–13)
P
enetrating keratoplasty (PKP) is a surgical procedure with a high success rate, especially for noninflammatory indications such as corneal ectasia, in which 5-year graft survival rates of 90% to 98% are reported.1–6 Besides the indication for surgery, graft survival is also highly dependent on other factors, such as surgical technique, concomitant diseases, and quality and intensity of short- and long-term follow-up care.1–8
Received for publication April 18, 2013; revision received August 28, 2013; accepted August 29, 2013. Published online ahead of print October 31, 2013. From the Eye Department, Red Cross Hospital, Munich, Germany. The authors have no funding or conflicts of interest to disclose. Reprints: Barbara Koller, Eye Department, Red Cross Hospital, Helene-WeberAllee 19, 80637 München, Germany (e-mail: [email protected]). Copyright © 2013 by Lippincott Williams & Wilkins
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Visually impairing corneal disease requiring corneal grafting may be associated with syndromes that go along with intellectual disability (ID), such as the Down syndrome.2,9,10 Especially in this patient subgroup, concomitant diseases with negative impact (eg, atopic dermatitis) or behavioral issues (such as aggressive eye rubbing) have been reported to reduce the long-term graft survival.2,8,9,11,12 However, optical rehabilitation is important for quality of life, especially in reduced mental function.13–15 The prognosis of corneal procedures in this patient population has been evaluated in only a few reports, and all of them include surgical procedures dating back to the 1970s and 1980s, and only single reports include cases operated on from the year 2000 onward.2,8,9,12,15,16 The purpose of this study was to analyze the outcome of all keratoplasty procedures in patients with ID, who had been treated at our institution over the past 20 years, in which we used the same surgical standard.
PATIENTS AND METHODS Patients All patients with ID who had undergone a keratoplasty procedure between January 1, 1991, and December 31, 2010, at the Eye Department, Red Cross Hospital, Munich, were identified retrospectively through the computerized database of the institution (Informed X.9.8; Informed GmbH, EfringenKirchen, Germany). For this, all patients who underwent a keratoplasty procedure performed under general anesthesia were considered to be eligible. The charts of all identified patients were checked manually for evidence of ID mainly by identifying the diagnosis of Down syndrome and/or evidence of a legal guardian, together with the legal status of being “mentally handicapped” (obvious from a state disability identification card entitling them to public support and benefits for participation in community life). All the eligible patients were not able to lead an independent life, living either in an institution (n = 9) or with their families (n = 20). According to the criteria of the World Health Organization, all the patients were moderately to severely handicapped.17 From these cases, the following data were transferred into an Excel sheet: name, first name, date of birth, date of surgery, ophthalmological history, general history, intraoperative and postoperative complications, additional surgical interventions, and the date of the last visit. All the patients were then invited for a follow-up visit by phone. Whenever this was not possible, the available information was retrieved from the patient’s chart or the treating ophthalmologist. Cornea Volume 33, Number 1, January 2014
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Surgical Technique Transplants were prepared either with a manual trephine (diameter $8.5 mm, Neuhann trephine; Geuder AG, Heidelberg, Germany) or with the guided trephine system (Krumeich GTS, diameter 7.5–8.5 mm; Polytech Ophthalmologie GmbH, Robdorf, Germany). After trephination of the recipient with either a motor trephine (diameter $8.5 mm, Neuhann trephine; Geuder AG) or the Krumeich GTS, the graft was fixated with 16 single sutures or 2 running double nontorque sutures (10-0 Nylon). All the patients were referred back to their ophthalmologist after the procedure was performed and were only seen for suture removal after 12 and 15 months and in cases of any postoperative problems. The postoperative standard medication consisted of dexamethasone phosphate given 4 times a day tapered over 6 months and artificial tears applied 4 times a day. After 6 months, local steroids were discontinued unless an episode of rejection occurred. In the case of a rejection, the frequency of applying topical steroids was increased to an hourly interval and/or betamethasone was administered subconjunctivally. In cases of a repeat keratoplasty after a rejection, oral immunosuppressive therapy was administered, consisting of either oral prednisolone (starting at 1 mg/kg) tapered typically over 6 months and/or oral mycophenolate mofetil (1 g twice daily) for 2 years, adjusted according to tolerance and clinical findings.
RESULTS During the study period, a total of 55 keratoplasty procedures on 40 eyes of 31 patients were performed. A total of 19 patients presented to the study institution for a followup examination upon invitation. Three patients had already died, and 9 patients were unable to present themselves because of failure to contact or because of uncooperative caregivers. These patients were included with the findings recorded in the chart from their last examination. Two cases were lost to any form of follow-up and were excluded from further analysis, leaving 38 eyes from 29 patients with 53 keratoplasty procedures for the final analysis. The median age at the time of the first keratoplasty procedure was 38 years (minimum 13, maximum 55). The median follow-up was for 9 years (minimum 6 months, maximum 20 years). A total of 31 eyes (82%) of 24 patients were followed up for .5 years and 18 eyes (47%) of 13 patients were followed up for .10 years.
Diagnosis In 20 patients, the general diagnosis was Down syndrome, 1 patient had an ID caused by brain tumor excision at the age of 13 years, and 8 patients had an ID of an unknown origin. The indication for the first PKP (n = 35) was keratoconus in 33 patients and corneal opacity caused by exposure in facial nerve palsy in 2 patients. A total of 13 keratoplasty procedures were performed on an emergency basis: spontaneous perforation in 1 patient, and acute hydrops (surgery within 3 weeks of the first presentation) in 12 patients. The reasons for the 18 repeat keratoplasty procedures (n = 8 eyes) were nonimmunological graft decompensation in Ó 2013 Lippincott Williams & Wilkins
Keratoplasty in Patients With ID
3 eyes (5, 6, and 11 years after the initial PKP), decompensation after graft rejection in 11 cases, therapy-resistant corneal melt because of a persistent ocular surface defect in 2 patients, and acute rejection with ulcer in 2 patients.
Prior Surgical Interventions In the 29 study patients, 6 eyes had undergone a PKP procedure elsewhere. In 3 of these eyes, a repeat keratoplasty for graft decompensation (2 cases after graft rejection) was performed as the first procedure at the study institution. These cases were considered as repeat keratoplasties for analysis.
Surgical Details
All, except 2 eyes, were phakic at the time of the first intervention. Five eyes underwent a triple procedure (crystalline lens extraction, intraocular lens implantation, and PKP). In the 2 eyes with facial nerve palsy, a permanent tarsorrhaphy was performed simultaneously. In 1 eye, a Descemet stripping endothelial keratoplasty was performed for graft decompensation, 11 years after the original PKP. All other procedures were PKPs.
Complications In the 53 keratoplasty procedures, there was 1 intraoperative complication recorded, that is, injury of the anterior lens capsule during trephination in 1 case of repeat keratoplasty in the case with corneal melt. Postoperative complications included secondary glaucoma in 5 eyes and at least 1 episode of graft rejection in 8 eyes (including 2 eyes with a history of bacterial corneal ulcer). One of the cases with facial nerve palsy was only seen for 6 months and had persistent epithelial defects. A total of 6% of the primary keratoplasties (n = 2/35) and 11% of all the cases (n = 4/38) were considered final “failures” (see below). The second case with facial nerve palsy developed a corneal ulcer with purulent endophthalmitis, which presented late, could not be managed conservatively, and underwent primary enucleation. Three other eyes (3 patients) with a history of rejection episodes/corneal ulcer underwent several repeat surgical procedures and remained with a failed graft because of graft rejection to date (see below).
Graft Survival Graft survival was defined as clear graft, failure as opacification, regardless of cause, and thus incompatible with useful vision, final failure referring to the status at the last follow-up visit. The graft survival rate of the primary graft (excluding the 3 cases of repeat keratoplasty as the first procedure at the study institution) was 89% (n = 31/35) up to 27 months and 86% (n = 30/35) thereafter up to 11 years (Fig. 1). At the last follow-up visit, a clear graft was present in 89% of all the cases (n = 34/38).
Functional Results In those eyes with complete preoperative and postoperative visual acuity recordings (n = 21), the median www.corneajrnl.com |
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FIGURE 1. Graph showing the Kaplan–Meier analysis of graft survival. Group 1: Survival of the primary graft transplanted in the study institution (n = 35). Group 2: Overall graft clarity of the same initial primary grafts (n = 35) at the last visit including regrafts (n = 10 in 5 eyes).
preoperative best-corrected visual acuity was 1.2 logarithm of the minimum angle of resolution (LogMAR; minimum 0.4, maximum 3). At the last follow-up visit, it had improved to a median of 0.7 LogMAR (minimum 0.2, maximum 3). Corneal topography at the last follow-up was available for 19 eyes (Pentacam; Oculus Optikgeräte, Wetzlar, Germany). The median topographic astigmatism was 2.9 diopters (minimum 0.4, maximum 10.6).
Further Surgical Procedures During the follow-up period in the 38 study eyes, 7 cataract surgeries were performed, including 1 case of simultaneous toric add-on intraocular lens implantation. One eye underwent a trabeculotomy and subsequent Ahmed Valve implantation for secondary glaucoma. One eye was enucleated (see above). A total of 31 eyes (including 1 repeat PKP as the first procedure in our institute) had no further corneal interventions after the first PKP procedure, 1 eye underwent a second PKP, and 1 eye underwent Descemet stripping endothelial keratoplasty (see above). Five other eyes (5 patients) underwent .2 PKP. Three eyes underwent a total of 3 PKP because of graft rejection and/or corneal ulcer. The remaining 2 eyes underwent a total of 4 and 5 penetrating keratoplasties, because of graft rejection and/or corneal ulcer.
DISCUSSION Several studies have shown that corneal diseases, especially keratoconus, frequently occur in patients with ID.9–11 The prevalence of keratoconus in this patient group has been estimated to be between 2.3% and 7.5%,10,11 the prevalence in patients with the Down syndrome being even higher (3%–20%).8,9,11,18 Whether genetic alterations leading to structural and biochemical changes of the cornea or external
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factors, such as extensive eye rubbing, are responsible for this, or a combination of both, is unclear.11 Optical rehabilitation must be considered especially important in patients with ID to ensure physical and mental well-being and optimize self-dependence.15 Even though in our study we did not evaluate the level of visual acuity required for this, our impression was that patients who had a visual acuity of $0.3 (#0.5 LogMAR) uniformly got along well in daily life, often denying further optical aids to improve this vision level. The results of our study demonstrate that the majority of the patients with ID will benefit from corneal grafting, which is contrary to the commonly encountered opinion that these patients do poorly.2 The median visual acuity (representing the majority of patients) improved after the surgical procedure. Even though the values of visual acuity are clearly below the levels in standard cases of keratoplasty for ectatic corneal disease with comparable surgical technique,5,6,16,19 one must consider the differing initial situation (eg, advanced pathology) and possible cooperation deficits in refraction/ visual acuity testing. The latter may be corroborated by the fact, that the mean postoperative topographic cylinder (2.9 diopters) was comparable or lower than in comparable standard keratoplasty cases.5,6,18 Considering only the primary grafts, the survival in this series was 86% from 2 years up to .11 years. These results compare favorably with 2 other recent series in patients with ID by García, García and Martínez8 (82.14% clear graft at the last visit) and Wroblewski et al15 (83% clear graft after 3 years). However, there are also a number of earlier series that reported lower success rates.2,12,16 Reasons for the overall poorer outcome, as compared with standard keratoplasty procedures (5-year survival in corneal ectatic disease, 90%–98%),1–6 have been proposed to be a high number of interventions on an emergency basis and/or the presence of concomitant problems such as lid anomalies, advanced findings such as hydrops, corneal infections, and (self-inflicted) trauma.2,6,9,12,15,16 This corresponds to our series, including 2 cases of facial nerve palsy and 12 cases with acute hydrops. The latter had severe discomfort and did not feel/were not considered by their caregivers capable to await resolution of the edema, which is generally the preferred approach.6,8 In none of these cases, however, did a final failure occur. These concomitant problems may also explain the relatively high rejection rate in our study (21%), which is higher than that reported for comparable standard keratoplasty cases.3,5,6,18 Because ID often causes a lack of communication, which may lead to a delay in timely awareness and diagnosis of complications, this condition may even be underreported.2,9,15 In this context, the quality of the postoperative care has been reported to play an important role in the long-term outcome.2,8,15 Superior academic training of the caregivers and patients with postoperative care at home has been reported to do better in the study by García, García and Martínez.8 In our study, we did not evaluate the level of quality of the postoperative care, which may also be difficult to assess in a standardized way. Therefore, from our study we cannot draw conclusions whether (and which) postoperative factors were associated with a reduced outcome, even though this Ó 2013 Lippincott Williams & Wilkins
Cornea Volume 33, Number 1, January 2014
seems likely. From our impression, however, the individual diligence of the caregivers, which can be positively influenced by training as shown by García, García and Martínez8 rather than the level of their academic degree, has an influence on the outcome. In our study, there is no indirect evidence of a relation of intelligence level of patients and outcome, because only 2 out of the 4 final failures in our series occurred in patients who were disabled to a level where refraction or visual acuity testing was not possible. Other authors have found a relation between a lower intelligence level and reduced outcome, however, without the ability to distinguish whether the intelligence level or associated behavioral issues account for this.8,12 Actually, conclusions on the impact of ID itself, associated ocular pathologies (including genetic tissue alterations), or behavioral issues on the outcome/number and kind of complications can only be drawn in the presence of a matched control group (of normal intellect). This, however, is particularly difficult, because of the small overall number of patients with ID in combination with a high percentage of advanced pathology in these cases. Haugen et al12 proposed epikeratophakia as a surgical option for corneal disease in ID, because of the low complication rate with this procedure, leaving PKP only for patients with a higher intellectual status. Because we have, for a variety of reasons, never used epikeratophakia for the surgical treatment of keratoconus, we cannot contribute to this discussion. Because of the advances in deep anterior lamellar grafting techniques,20 this technique is no longer used to a noteworthy extent. The new lamellar corneal transplant techniques and their further development contain great promise to improve the overall prognosis in the patient subgroup with ID. In conclusion, it is to be noted that the long-term graft survival after a PKP in patients with ID is lower than in comparable standard PKP-operated patients.1–6,16 The majority of patients with ID, however, eventually retain a long-term clear graft and will achieve an increase in visual acuity. Keratoplasty in these individuals can be considered whenever patients can no longer comply with the visual demands of their particular individual life. The further development of lamellar grafting techniques may improve the overall outcome also in this patient group. The exact influence of associated factors on the outcome, such as the initial situation (eg, hydrops) and postoperative parameters (eg, eye rubbing, caregivers’ diligence) can reliably only be assessed in a prospective study with clearly defined and standardized outcome measures.
Ó 2013 Lippincott Williams & Wilkins
Keratoplasty in Patients With ID
ACKNOWLEDGMENTS The authors thank Dr. Marco Bornhauser, FEBO, for critical revision of this article. REFERENCES 1. Fasolo A, Capuzzo C, Fornea M, et al. Risk factors for graft failure after penetrating keratoplasty: 5-year follow-up from the corneal transplant epidemiological study. Cornea. 2011;30:1328–1335. 2. Völker-Dieben HJ, Odenthal MT, D’Amaro J, et al. Surgical treatment of corneal pathology in patients with Down’s syndrome. J Intellect Disabil Res. 1993;37:169–175. 3. Thompson RW Jr, Price MO, Bowers PJ, et al. Long-term graft survival after penetrating keratoplasty. Ophthalmology. 2003;110:1396–1402. 4. Borderie VM, Boëlle PY, Touzeau O, et al. Predicted long-term outcome of corneal transplantation. Ophthalmology. 2009;116:2354–2360. 5. Zhang YM, Wu SQ, Yao YF. Long-term comparison of full-bed deep anterior lamellar keratoplasty and penetrating keratoplasty in treating keratoconus. J Zhejiang Univ Sci B. 2013;14:438–450. 6. Basu S, Reddy JC, Vaddavalli PK, et al. Long-term outcomes of penetrating keratoplasty for keratoconus with resolved corneal hydrops. Cornea. 2012;31:615–620. 7. Reinhard T, Möller M, Sundmacher R. Penetrating keratoplasty in patients with atopic dermatitis with and without systemic cyclosporin A. Cornea. 1999;18:645–651. 8. García García GP, Martínez JB. Outcomes of penetrating keratoplasty in mentally retarded patients with keratoconus. Cornea. 2008;27:980–987. 9. McElvanney AM, Adhikary HP. Penetrating keratoplasty in the mentally retarded. Eye (Lond). 1997;11:786–789. 10. van Splunder J, Stilma JS, Bernsen RM, et al. Prevalence of ocular diagnoses found on screening 1539 adults with intellectual disabilities. Ophthalmology. 2004;111:1457–1463. 11. Haugen OH. Keratoconus in the mentally retarded. Acta Ophthalmol (Copenh). 1992;70:111–114. 12. Haugen OH, Høvding G, Eide GE, et al. Corneal grafting for keratoconus in mentally retarded patients. Acta Ophthalmol Scand. 2001;79:609–615. 13. Küchle M, Naumann GO. Penetrating keratoplasty for keratoconus in trisomy 21 [in German]. Klin Monbl Augenheilkd. 1992;200:228–230. 14. Isralowitz R, Madar M, Lifshitz T, et al. Visual problems among people with mental retardation. Int J Rehabil Res. 2003;26:149–152. 15. Wroblewski KJ, Mader TH, Torres MF, et al. Long-term graft survival in patients with Down syndrome after penetrating keratoplasty. Cornea. 2006;25:1026–1028. 16. Bodenmueller M, Goldblum D, Frueh BE. Penetrating keratoplasty in Down’s syndrome [in German]. Klin Monbl Augenheilkd. 2003;220: 99–102. 17. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva, Switzerland: World Health Organization; 1992. 18. Gaynon MW, Schimek RA. Down’s syndrome: a ten-year group study. Ann Ophthalmol. 1977;9:1493–1497. 19. Ruhswurm I, Scholz U, Pfleger T, et al. Three-year clinical outcome after penetrating keratoplasty for keratoconus with the guided trephine system. Am J Ophthalmol. 1999;127:666–673. 20. Sarnicola V, Toro P, Sarnicola C, et al. Long-term graft survival in deep anterior lamellar keratoplasty. Cornea. 2012;31:621–626.
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