Penetrating Keratoplasty for Corneal Amyloidosis in Familial Amyloidosis, Finnish Type Jaakko S. Mattila, MD, Kari Krootila, MD, PhD, Tero Kivelä, MD, PhD, Juha M. Holopainen, MD, PhD Purpose: To analyze the outcome of penetrating keratoplasty (PK) to the first eye for corneal amyloidosis in familial amyloidosis, Finnish type (FAF). Design: Single-center, retrospective, nonrandomized, interventional, noncomparative case series. Participants: Thirty-one eyes of 31 patients with FAF. Intervention: All patients with FAF who had their first PK in Helsinki University Eye Hospital between January 1, 1990, and August 1, 2011, were identified and a retrospective analysis of the patient charts was performed. Main Outcome Measures: Best spectacle-corrected visual acuity (BCVA), intraoperative and postoperative complications, graft survival, reason for graft failure, and frequency of regrafting. Results: The median follow-up period was 32 months (range, 5e114). After 24 months, the median BCVA was 1.15 on a logarithm of the minimum angle of resolution scale (20/280; mean, 1.1; SD, 0.5) in comparison with the preoperative median BCVA of 1.3 (20/400; mean, 1.3; SD, 0.4). At 24 months, 3 of 18 eyes (17%) had a visual acuity of 0.5 (20/63) and 13 of 18 grafts (72%) were clear. Rejection occurred in 6 of 31 primary grafts (19%). Graft failure occurred in 16 of 31 eyes and resulted from surface complications in 11 eyes and additionally from rejection in 5 eyes. Seven eyes needed regrafting (twice in 1 eye). Complications were frequent in the early and late postoperative periods. Presence of preoperative corneal or graft neovascularization was an indicator of a high risk of graft failure and poor visual outcome. Conclusions: In a minority of FAF patients, PK improves vision. Owing to the high failure risk and guarded visual prognosis after PK, it is important that both the surgeon and the patient have realistic expectations. It may be reasonable to limit PK to cases with bilateral advanced disease. It seems reasonable to optimize ocular surface health and to delay PK. Ophthalmology 2015;122:457-463 ª 2015 by the American Academy of Ophthalmology. Supplementary material is available online at www.aaojournal.org.
Amyloidosis refers to a clinically polymorphous group of inherited and sporadic disorders in which protein aggregates known as amyloid are deposited into the affected tissues.1 Some degree of local deposition of amyloid is part of normal human aging,2,3 but excessive deposition can disrupt the normal function of tissues. Familial amyloidosis, Finnish type (FAF; OMIM 105120) is an autosomal-dominant condition that is part of Finnish disease heritage and is also known as Meretoja syndrome or hereditary gelsolin amyloidosis. The corneal manifestation of FAF was previously known as lattice corneal dystrophy, type II, or gelsolin type lattice corneal dystrophy, but it is no longer considered a dystrophy, because FAF is a systemic amyloidosis. In Finland, FAF is among the most common inherited diseases and affects 400e600 Finns.4e6 The syndrome has been reported from several European countries, Japan, Iran, and the United States, and thus it is not exclusive for Finnish disease heritage.5,7e23 Familial amyloidosis, Finnish type, arises from a G654A (Finnish type) or G654T (Danish type) point mutation in the gelsolin (GSN) gene on chromosome 9q33. 2015 by the American Academy of Ophthalmology Published by Elsevier Inc.
Gelsolin is an 83-kDa actin-modulating protein24 synthesized in most types of cells and tissues. The role of gelsolin in the normal human cornea remains unknown, but it may function in binding and removing actin. In FAF, aberrant degradation of mutated gelsolin causes formation of a 7kDa degradation product leading to amyloid aggregation.25 In FAF, the mutated protein is deposited widely in different parts of the eye.26e28 Usually, the corneal manifestation of FAF develops first.5,29 The distribution of corneal deposits in the cornea is pathognomonic and accordingly the diagnosis of FAF can be made by histological analysis at the time of corneal transplantation.27 Immunohistochemical studies in patients with FAF27,28,30 show strands of amyloid in the anterior and midstroma, deposition of a continuous layer of amyloid under Bowman’s layer and occasionally at the level of the epithelial basement membrane, and secondary scarring with occasional amyloid deposits invading the subepithelial space.27 The subepithelial deposits rather than the lattice lines lead to recurrent corneal erosions and eventual loss of vision requiring corneal transplantation in FAF. http://dx.doi.org/10.1016/j.ophtha.2014.09.035 ISSN 0161-6420/14
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Ophthalmology Volume 122, Number 3, March 2015
Figure 1. A, Typical clinical facial image of a familial amyloidosis, Finnish type (FAF) patient. This patient had several oculoplastic operations to correct lid malposition. B, Corneal image before penetrating keratoplasty showing poor quality of the corneal surface, diffuse corneal scarring, and amyloid deposition. C, Clinical corneal photograph after penetrating keratoplasty. The image shows leather-like and thickened corneal epithelium after a long-lasting, persistent erosion.
The diagnosis of FAF can be confirmed with genetic testing.6 In advanced disease, patients suffer from corneal epithelial erosions and neurotrophic keratitis because of corneal sensory nerve damage,31 visual acuity decreases, and FAF can lead to corneal blindness.4,5 The visual acuity usually remains adequate until the seventh decade,32 at which time it often deteriorates because of loss of corneal transparency. Advanced corneal opacification can be treated only by keratoplasty, usually with penetrating keratoplasty (PK). However, the efficacy and safety of this intervention remain unknown. Specifically, FAF affects cranial nerves and neuropathy of the facial nerve is a typical finding. Other neuropathies are also found and sensory defects of the cornea and the face are clinically significant.6,31,33e37 Blepharochalasis, entropion, ectropion, and lagophthalmus are frequent6 and complicate the management of ocular surface diseases. Figure 1 shows a typical clinical presentation of a FAF patient. It is believed that all lattice dystrophies have a similar and generally favorable prognosis after PK.38 However, only 1 case report of a patient with FAF who had a previous PK has been published.39 The patient had received 4 keratoplasties in 3 years, roughly after the age of 40, and a fifth keratoplasty 10 years later. The use of keratoplasty in the treatment of FAF has not been evaluated systematically. In Finland, nearly all FAF patients undergoing corneal transplantation are treated at the Helsinki University Eye Hospital. Over the years, we have observed that advanced corneal lattice-like amyloidosis in FAF is challenging to
458
treat. We performed a retrospective analysis of consecutive PK surgeries for FAF.
Methods This study was reviewed by the Helsinki-Uusimaa Hospital District ethics committee and followed the tenets of the Declaration of Helsinki. We analyzed the patient records of all FAF patients that underwent first PK at the Helsinki University Eye Hospital between January 1, 1990, and August 1, 2011. The diagnosis of FAF was verified by typical histopathology of excised corneal disks together with characteristic facial features, typical age relative to the stage of disease, and a positive family history. Most patients were also referred from Kymenlaakso, a region with a high prevalence of FAF. One patient had additional confirmation of the diagnosis through genetic testing. The only exclusion criterion was a follow-up period of 0.25 mm in the remaining 11 eyes. A single continuous 10-0 nylon suture was used alone in 22 eyes (71%) and in combination with a continuous 11-0 nylon suture in 7 eyes (23%), a continuous 10-0 nylon suture with single sutures was used in 1 eye, and interrupted 10-0 nylon sutures were used in 1 eye. At the time of the primary PK, simultaneous extracapsular cataract extraction with intraocular lens (IOL) implantation was performed in 6 eyes and phacoemulsification with IOL implantation in 7 eyes. Tarsorraphy at the end of the surgery was performed in 5 cases. Topical antibiotics were administered for a median of 2 months (range, 1e12) after PK. The antibiotics were continued for such a long period because of frequent persistent epithelial defects (Table 1). Topical corticosteroids were used for 3 months and tapered off. All patients were reviewed on the first postoperative day and then on an individual basis (mean, 14 visits; range, 3e47) during the first postoperative year.
Intraoperative and Postoperative Complications No intraoperative complications were observed except for 1 posterior capsule rupture during combined phacoemulsification. A high number of early and late postoperative complications were noted (Table 1). The most frequent complications were related to the corneal epithelium. Epithelialization was noted at a median of 1 day (mean, 6; SD, 9; range, 1e34) after PK, but in 7 eyes the epithelialization was delayed. For these the graft epithelialized by day 7 or later. Overall graft survival was compromised by frequent surface complications and graft rejections leading to graft failures (Fig 2A).
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Ophthalmology Volume 122, Number 3, March 2015
Figure 2. A, Causes of graft failure for primary, second, and third grafts over the full follow-up. B, Best-corrected visual acuity in logarithm of the minimum angle of resolution after primary penetrating keratoplasty for corneal dystrophy owing to familial amyloidosis, Finnish type.
Subsequent Surgeries Postoperative tarsorraphy became necessary in 11 eyes (35%), an amniotic membrane transplantation in 1 eye (3%), and a combined tarsorraphy and amniotic membrane transplantation in 2 eyes (6%). Six transplants had to be resutured because of wound leakage, 1 in combination with amniotic membrane transplantation. Surgical eyelash epilation was performed in 3 eyes, 2 eyes received punctal plugs, 2 eyes received upper lid gold weights, and 5 miscellaneous oculoplastic surgeries were performed. One eye underwent laser cyclophotocoagulation and 1 eye was eviscerated after a Pseudomonas keratitis led to a purulent endophthalmitis. Subsequent extracapsular cataract extraction was performed in 1 eye and phacoemulsification in 5 eyes, all with IOL implantation. Nd:YAG laser posterior capsulotomy was performed on 2 eyes, relaxing corneal incisions were performed on 4 eyes, compressing sutures on 1 eye, and a SulcoFlex add-on IOL (Rayner, East Sussex, UK) was implanted in 1 eye. Repeat PK was performed in 7 eyes and a third PK was done once with an unfavorable outcome.
(20/400; mean, 1.3; SD, 0.4). Eighteen eyes remained under followup at 24 months and had a median BCVA of 1.15 (20/280; mean, 1.1; SD, 0.5). The change in BCVA was significant (P ¼ 0.03, paired t test). By 24 months, 3 of the 18 eyes (17%) had a BCVA of 0.5 (20/63) and 12 (77%) had a BCVA that was a mutation of the gelsolin gene in Finnish families and an unrelated American family. Genomics 1992;13:898–901. 11. Sunada Y, Shimizu T, Mannen T, Kanazawa I. Familial amyloidotic polyneuropathy type IV (Finnish type)ethe first description of a large kindred in Japan [in Japanese]. Rinsho Shinkeigaku 1992;32:826–33. 12. Stewart HS, Parveen R, Ridgway AE, et al. Late onset lattice corneal dystrophy with systemic familial amyloidosis, amyloidosis V, in an English family. Br J Ophthalmol 2000;84:390–4. 13. Rothstein A, Auran JD, Wittpenn JR, et al. Confocal microscopy in Meretoja syndrome. Cornea 2002;21:364–7. 14. Conceicao I, Sales-Luis ML, De Carvalho M, et al. Gelsolinrelated familial amyloidosis, Finnish type, in a Portuguese family: clinical and neurophysiological studies. Muscle Nerve 2003;28:715–21. 15. Chastan N, Baert-Desurmont S, Saugier-Veber P, et al. Cardiac conduction alterations in a French family with amyloidosis of the Finnish type with the p.Asp187Tyr mutation in the GSN gene. Muscle Nerve 2006;33:113–9. 16. Huerva V, Velasco A, Sanchez MC, et al. Lattice corneal dystrophy type II: clinical, pathologic, and molecular study in a Spanish family. Eur J Ophthalmol 2007;17:424–9. 17. Ardalan MR, Shoja MM, Kiuru-Enari S. Amyloidosis-related nephrotic syndrome due to a G654A gelsolin mutation: the first report from the Middle East. Nephrol Dial Transplant 2007;22:272–5. 18. Burmann J, Fassbender K, Henn W, et al. Neurological manifestations of AGel amyloidosis (Meretoja’s syndrome) in a German family [in German]. Fortschr Neurol Psychiatr 2011;79:238–41. 19. Maramattom BV, Chickabasaviah YT. A new Indian family affected by gelsolin amyloidosis [letter]. Neurol India 2013;61: 673–5. 20. Donders PC, Blanksma LJ. Meretoja syndrome: lattice dystrophy of the cornea with hereditary generalized amyloidosis. Ophthalmologica 1979;178:173–80. 21. Papathanassiou M, Liarakos VS, Vaikousis E, et al. Corneal melt in lattice corneal dystrophy type II after cataract surgery. J Cataract Refract Surg 2009;35:185–9. 22. Maury CP, Liljestrom M, Boysen G, et al. Danish type gelsolin related amyloidosis: 654G-T mutation is associated with a disease pathogenetically and clinically similar to that caused by the 654G-A mutation (familial amyloidosis of the Finnish type). J Clin Pathol 2000;53:95–9. 23. Solari HP, Ventura MP, Antecka E, et al. Danish type gelsolinrelated amyloidosis in a Brazilian family: case reports. Arq Bras Oftalmol 2011;74:286–8. 24. Chaponnier C, Janmey PA, Yin HL. The actin filament-severing domain of plasma gelsolin. J Cell Biol 1986;103:1473–81. 25. Maury CP, Nurmiaho-Lassila EL. Creation of amyloid fibrils from mutant Asn187 gelsolin peptides. Biochem Biophys Res Commun 1992;183:227–31. 26. Haltia M, Ghiso J, Prelli F, et al. Amyloid in familial amyloidosis, Finnish type, is antigenically and structurally related to gelsolin. Am J Pathol 1990;136:1223–8. 27. Kivela T, Tarkkanen A, McLean I, et al. Immunohistochemical analysis of lattice corneal dystrophies types I and II. Br J Ophthalmol 1993;77:799–804. 28. Kivela T, Tarkkanen A, Frangione B, et al. Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja’s syndrome. Invest Ophthalmol Vis Sci 1994;35:3759–69.
Mattila et al
Penetrating Keratoplasty in FAF
29. Meretoja J. Inherited systemic amyloidosis with lattice corneal dystrophy [dissertation]. Helsinki, Finland: Department of Ophthalmology, University of Helsinki; 1973. 30. Loeffler KU, Edward DP, Tso MO. An immunohistochemical study of gelsolin immunoreactivity in corneal amyloidosis. Am J Ophthalmol 1992;113:546–54. 31. Rosenberg ME, Tervo TM, Gallar J, et al. Corneal morphology and sensitivity in lattice dystrophy type II (familial amyloidosis, Finnish type). Invest Ophthalmol Vis Sci 2001;42:634–41. 32. Meretoja J. Comparative histopathological and clinical findings in eyes with lattice corneal dystrophy of two different types. Ophthalmologica 1972;165:15–37. 33. Kiuru S, Seppalainen AM. Neuropathy in familial amyloidosis, Finnish type (FAF): electrophysiological studies. Muscle Nerve 1994;17:299–304. 34. Kiuru S, Matikainen E, Kupari M, et al. Autonomic nervous system and cardiac involvement in familial amyloidosis, Finnish type (FAF). J Neurol Sci 1994;126:40–8. 35. Kiuru S, Salonen O, Haltia M. Gelsolin-related spinal and cerebral amyloid angiopathy. Ann Neurol 1999;45:305–11. 36. Kiuru-Enari S, Somer H, Seppalainen AM, et al. Neuromuscular pathology in hereditary gelsolin amyloidosis. J Neuropathol Exp Neurol 2002;61:565–71.
37. Kiuru-Enari S, Keski-Oja J, Haltia M. Cutis laxa in hereditary gelsolin amyloidosis. Br J Dermatol 2005;152:250–7. 38. De Sousa LB, Mannis MJ. The stromal dystrophies. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea vol 1. 2nd ed. Philadelphia: Elsevier/Mosby; 2005:907–27. 39. Carrwik C, Stenevi U. Lattice corneal dystrophy, gelsolin type (Meretoja’s syndrome). Acta Ophthalmol 2009;87: 813–9. 40. Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C. Neurotrophic influences on corneal epithelial cells. Exp Eye Res 1994;59:597–605. 41. Guilbert E, Bullet J, Sandali O, et al. Long-term rejection incidence and reversibility after penetrating and lamellar keratoplasty. Am J Ophthalmol 2013;155:560–9. 42. Wagoner MD, Ba-Abbad R, Al-Mohaimeed M, et al; King Khaled Eye Specialist Hospital Corneal Transplant Study Group. Postoperative complications after primary adult optical penetrating keratoplasty: Prevalence and impact on graft survival. Cornea 2009;28:385–94. 43. Bachmann B, Taylor RS, Cursiefen C. Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: an evidence-based meta-analysis. Ophthalmology 2010;117:1300–5.
Footnotes and Financial Disclosures Originally received: June 17, 2014. Final revision: September 20, 2014. Accepted: September 28, 2014. Available online: November 13, 2014.
The authors have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2014-951.
The Helsinki University Eye Hospital, University of Helsinki, Helsinki, Finland. Presented at: The 2014 World Ophthalmology Congress, Tokyo, Japan. Financial Disclosure(s): The Finnish Eye Foundation, the Evald and Hilda Nissi Foundation, the Finnish Ophthalmological Society and the Finnish Eye and Tissue Bank Foundation, Helsinki, Finland. The funding organizations had no role in the design or conduct of this research.
Abbreviations and Acronyms: BCVA ¼ best-corrected visual acuity; FAF ¼ familial amyloidosis, Finnish type; IOL ¼ intraocular lens; logMAR ¼ logarithm of the minimum angle of resolution; PK ¼ penetrating keratoplasty. Correspondence: Juha M. Holopainen, MD, PhD, Helsinki Eye Lab, Department of Ophthalmology, Helsinki University Eye Hospital, Haartmaninkatu 4 C, 00290 Helsinki, Finland. E-mail: juha.holopainen@hus.fi.
463
Amyloidosis refers to a clinically polymorphous group of inherited and sporadic disorders in which protein aggregates known as amyloid are deposited into the affected tissues.1 Some degree of local deposition of amyloid is part of normal human aging,2,3 but excessive deposition can disrupt the normal function of tissues. Familial amyloidosis, Finnish type (FAF; OMIM 105120) is an autosomal-dominant condition that is part of Finnish disease heritage and is also known as Meretoja syndrome or hereditary gelsolin amyloidosis. The corneal manifestation of FAF was previously known as lattice corneal dystrophy, type II, or gelsolin type lattice corneal dystrophy, but it is no longer considered a dystrophy, because FAF is a systemic amyloidosis. In Finland, FAF is among the most common inherited diseases and affects 400e600 Finns.4e6 The syndrome has been reported from several European countries, Japan, Iran, and the United States, and thus it is not exclusive for Finnish disease heritage.5,7e23 Familial amyloidosis, Finnish type, arises from a G654A (Finnish type) or G654T (Danish type) point mutation in the gelsolin (GSN) gene on chromosome 9q33. 2015 by the American Academy of Ophthalmology Published by Elsevier Inc.
Gelsolin is an 83-kDa actin-modulating protein24 synthesized in most types of cells and tissues. The role of gelsolin in the normal human cornea remains unknown, but it may function in binding and removing actin. In FAF, aberrant degradation of mutated gelsolin causes formation of a 7kDa degradation product leading to amyloid aggregation.25 In FAF, the mutated protein is deposited widely in different parts of the eye.26e28 Usually, the corneal manifestation of FAF develops first.5,29 The distribution of corneal deposits in the cornea is pathognomonic and accordingly the diagnosis of FAF can be made by histological analysis at the time of corneal transplantation.27 Immunohistochemical studies in patients with FAF27,28,30 show strands of amyloid in the anterior and midstroma, deposition of a continuous layer of amyloid under Bowman’s layer and occasionally at the level of the epithelial basement membrane, and secondary scarring with occasional amyloid deposits invading the subepithelial space.27 The subepithelial deposits rather than the lattice lines lead to recurrent corneal erosions and eventual loss of vision requiring corneal transplantation in FAF. http://dx.doi.org/10.1016/j.ophtha.2014.09.035 ISSN 0161-6420/14
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Ophthalmology Volume 122, Number 3, March 2015
Figure 1. A, Typical clinical facial image of a familial amyloidosis, Finnish type (FAF) patient. This patient had several oculoplastic operations to correct lid malposition. B, Corneal image before penetrating keratoplasty showing poor quality of the corneal surface, diffuse corneal scarring, and amyloid deposition. C, Clinical corneal photograph after penetrating keratoplasty. The image shows leather-like and thickened corneal epithelium after a long-lasting, persistent erosion.
The diagnosis of FAF can be confirmed with genetic testing.6 In advanced disease, patients suffer from corneal epithelial erosions and neurotrophic keratitis because of corneal sensory nerve damage,31 visual acuity decreases, and FAF can lead to corneal blindness.4,5 The visual acuity usually remains adequate until the seventh decade,32 at which time it often deteriorates because of loss of corneal transparency. Advanced corneal opacification can be treated only by keratoplasty, usually with penetrating keratoplasty (PK). However, the efficacy and safety of this intervention remain unknown. Specifically, FAF affects cranial nerves and neuropathy of the facial nerve is a typical finding. Other neuropathies are also found and sensory defects of the cornea and the face are clinically significant.6,31,33e37 Blepharochalasis, entropion, ectropion, and lagophthalmus are frequent6 and complicate the management of ocular surface diseases. Figure 1 shows a typical clinical presentation of a FAF patient. It is believed that all lattice dystrophies have a similar and generally favorable prognosis after PK.38 However, only 1 case report of a patient with FAF who had a previous PK has been published.39 The patient had received 4 keratoplasties in 3 years, roughly after the age of 40, and a fifth keratoplasty 10 years later. The use of keratoplasty in the treatment of FAF has not been evaluated systematically. In Finland, nearly all FAF patients undergoing corneal transplantation are treated at the Helsinki University Eye Hospital. Over the years, we have observed that advanced corneal lattice-like amyloidosis in FAF is challenging to
458
treat. We performed a retrospective analysis of consecutive PK surgeries for FAF.
Methods This study was reviewed by the Helsinki-Uusimaa Hospital District ethics committee and followed the tenets of the Declaration of Helsinki. We analyzed the patient records of all FAF patients that underwent first PK at the Helsinki University Eye Hospital between January 1, 1990, and August 1, 2011. The diagnosis of FAF was verified by typical histopathology of excised corneal disks together with characteristic facial features, typical age relative to the stage of disease, and a positive family history. Most patients were also referred from Kymenlaakso, a region with a high prevalence of FAF. One patient had additional confirmation of the diagnosis through genetic testing. The only exclusion criterion was a follow-up period of 0.25 mm in the remaining 11 eyes. A single continuous 10-0 nylon suture was used alone in 22 eyes (71%) and in combination with a continuous 11-0 nylon suture in 7 eyes (23%), a continuous 10-0 nylon suture with single sutures was used in 1 eye, and interrupted 10-0 nylon sutures were used in 1 eye. At the time of the primary PK, simultaneous extracapsular cataract extraction with intraocular lens (IOL) implantation was performed in 6 eyes and phacoemulsification with IOL implantation in 7 eyes. Tarsorraphy at the end of the surgery was performed in 5 cases. Topical antibiotics were administered for a median of 2 months (range, 1e12) after PK. The antibiotics were continued for such a long period because of frequent persistent epithelial defects (Table 1). Topical corticosteroids were used for 3 months and tapered off. All patients were reviewed on the first postoperative day and then on an individual basis (mean, 14 visits; range, 3e47) during the first postoperative year.
Intraoperative and Postoperative Complications No intraoperative complications were observed except for 1 posterior capsule rupture during combined phacoemulsification. A high number of early and late postoperative complications were noted (Table 1). The most frequent complications were related to the corneal epithelium. Epithelialization was noted at a median of 1 day (mean, 6; SD, 9; range, 1e34) after PK, but in 7 eyes the epithelialization was delayed. For these the graft epithelialized by day 7 or later. Overall graft survival was compromised by frequent surface complications and graft rejections leading to graft failures (Fig 2A).
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Ophthalmology Volume 122, Number 3, March 2015
Figure 2. A, Causes of graft failure for primary, second, and third grafts over the full follow-up. B, Best-corrected visual acuity in logarithm of the minimum angle of resolution after primary penetrating keratoplasty for corneal dystrophy owing to familial amyloidosis, Finnish type.
Subsequent Surgeries Postoperative tarsorraphy became necessary in 11 eyes (35%), an amniotic membrane transplantation in 1 eye (3%), and a combined tarsorraphy and amniotic membrane transplantation in 2 eyes (6%). Six transplants had to be resutured because of wound leakage, 1 in combination with amniotic membrane transplantation. Surgical eyelash epilation was performed in 3 eyes, 2 eyes received punctal plugs, 2 eyes received upper lid gold weights, and 5 miscellaneous oculoplastic surgeries were performed. One eye underwent laser cyclophotocoagulation and 1 eye was eviscerated after a Pseudomonas keratitis led to a purulent endophthalmitis. Subsequent extracapsular cataract extraction was performed in 1 eye and phacoemulsification in 5 eyes, all with IOL implantation. Nd:YAG laser posterior capsulotomy was performed on 2 eyes, relaxing corneal incisions were performed on 4 eyes, compressing sutures on 1 eye, and a SulcoFlex add-on IOL (Rayner, East Sussex, UK) was implanted in 1 eye. Repeat PK was performed in 7 eyes and a third PK was done once with an unfavorable outcome.
(20/400; mean, 1.3; SD, 0.4). Eighteen eyes remained under followup at 24 months and had a median BCVA of 1.15 (20/280; mean, 1.1; SD, 0.5). The change in BCVA was significant (P ¼ 0.03, paired t test). By 24 months, 3 of the 18 eyes (17%) had a BCVA of 0.5 (20/63) and 12 (77%) had a BCVA that was a mutation of the gelsolin gene in Finnish families and an unrelated American family. Genomics 1992;13:898–901. 11. Sunada Y, Shimizu T, Mannen T, Kanazawa I. Familial amyloidotic polyneuropathy type IV (Finnish type)ethe first description of a large kindred in Japan [in Japanese]. Rinsho Shinkeigaku 1992;32:826–33. 12. Stewart HS, Parveen R, Ridgway AE, et al. Late onset lattice corneal dystrophy with systemic familial amyloidosis, amyloidosis V, in an English family. Br J Ophthalmol 2000;84:390–4. 13. Rothstein A, Auran JD, Wittpenn JR, et al. Confocal microscopy in Meretoja syndrome. Cornea 2002;21:364–7. 14. Conceicao I, Sales-Luis ML, De Carvalho M, et al. Gelsolinrelated familial amyloidosis, Finnish type, in a Portuguese family: clinical and neurophysiological studies. Muscle Nerve 2003;28:715–21. 15. Chastan N, Baert-Desurmont S, Saugier-Veber P, et al. Cardiac conduction alterations in a French family with amyloidosis of the Finnish type with the p.Asp187Tyr mutation in the GSN gene. Muscle Nerve 2006;33:113–9. 16. Huerva V, Velasco A, Sanchez MC, et al. Lattice corneal dystrophy type II: clinical, pathologic, and molecular study in a Spanish family. Eur J Ophthalmol 2007;17:424–9. 17. Ardalan MR, Shoja MM, Kiuru-Enari S. Amyloidosis-related nephrotic syndrome due to a G654A gelsolin mutation: the first report from the Middle East. Nephrol Dial Transplant 2007;22:272–5. 18. Burmann J, Fassbender K, Henn W, et al. Neurological manifestations of AGel amyloidosis (Meretoja’s syndrome) in a German family [in German]. Fortschr Neurol Psychiatr 2011;79:238–41. 19. Maramattom BV, Chickabasaviah YT. A new Indian family affected by gelsolin amyloidosis [letter]. Neurol India 2013;61: 673–5. 20. Donders PC, Blanksma LJ. Meretoja syndrome: lattice dystrophy of the cornea with hereditary generalized amyloidosis. Ophthalmologica 1979;178:173–80. 21. Papathanassiou M, Liarakos VS, Vaikousis E, et al. Corneal melt in lattice corneal dystrophy type II after cataract surgery. J Cataract Refract Surg 2009;35:185–9. 22. Maury CP, Liljestrom M, Boysen G, et al. Danish type gelsolin related amyloidosis: 654G-T mutation is associated with a disease pathogenetically and clinically similar to that caused by the 654G-A mutation (familial amyloidosis of the Finnish type). J Clin Pathol 2000;53:95–9. 23. Solari HP, Ventura MP, Antecka E, et al. Danish type gelsolinrelated amyloidosis in a Brazilian family: case reports. Arq Bras Oftalmol 2011;74:286–8. 24. Chaponnier C, Janmey PA, Yin HL. The actin filament-severing domain of plasma gelsolin. J Cell Biol 1986;103:1473–81. 25. Maury CP, Nurmiaho-Lassila EL. Creation of amyloid fibrils from mutant Asn187 gelsolin peptides. Biochem Biophys Res Commun 1992;183:227–31. 26. Haltia M, Ghiso J, Prelli F, et al. Amyloid in familial amyloidosis, Finnish type, is antigenically and structurally related to gelsolin. Am J Pathol 1990;136:1223–8. 27. Kivela T, Tarkkanen A, McLean I, et al. Immunohistochemical analysis of lattice corneal dystrophies types I and II. Br J Ophthalmol 1993;77:799–804. 28. Kivela T, Tarkkanen A, Frangione B, et al. Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja’s syndrome. Invest Ophthalmol Vis Sci 1994;35:3759–69.
Mattila et al
Penetrating Keratoplasty in FAF
29. Meretoja J. Inherited systemic amyloidosis with lattice corneal dystrophy [dissertation]. Helsinki, Finland: Department of Ophthalmology, University of Helsinki; 1973. 30. Loeffler KU, Edward DP, Tso MO. An immunohistochemical study of gelsolin immunoreactivity in corneal amyloidosis. Am J Ophthalmol 1992;113:546–54. 31. Rosenberg ME, Tervo TM, Gallar J, et al. Corneal morphology and sensitivity in lattice dystrophy type II (familial amyloidosis, Finnish type). Invest Ophthalmol Vis Sci 2001;42:634–41. 32. Meretoja J. Comparative histopathological and clinical findings in eyes with lattice corneal dystrophy of two different types. Ophthalmologica 1972;165:15–37. 33. Kiuru S, Seppalainen AM. Neuropathy in familial amyloidosis, Finnish type (FAF): electrophysiological studies. Muscle Nerve 1994;17:299–304. 34. Kiuru S, Matikainen E, Kupari M, et al. Autonomic nervous system and cardiac involvement in familial amyloidosis, Finnish type (FAF). J Neurol Sci 1994;126:40–8. 35. Kiuru S, Salonen O, Haltia M. Gelsolin-related spinal and cerebral amyloid angiopathy. Ann Neurol 1999;45:305–11. 36. Kiuru-Enari S, Somer H, Seppalainen AM, et al. Neuromuscular pathology in hereditary gelsolin amyloidosis. J Neuropathol Exp Neurol 2002;61:565–71.
37. Kiuru-Enari S, Keski-Oja J, Haltia M. Cutis laxa in hereditary gelsolin amyloidosis. Br J Dermatol 2005;152:250–7. 38. De Sousa LB, Mannis MJ. The stromal dystrophies. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea vol 1. 2nd ed. Philadelphia: Elsevier/Mosby; 2005:907–27. 39. Carrwik C, Stenevi U. Lattice corneal dystrophy, gelsolin type (Meretoja’s syndrome). Acta Ophthalmol 2009;87: 813–9. 40. Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C. Neurotrophic influences on corneal epithelial cells. Exp Eye Res 1994;59:597–605. 41. Guilbert E, Bullet J, Sandali O, et al. Long-term rejection incidence and reversibility after penetrating and lamellar keratoplasty. Am J Ophthalmol 2013;155:560–9. 42. Wagoner MD, Ba-Abbad R, Al-Mohaimeed M, et al; King Khaled Eye Specialist Hospital Corneal Transplant Study Group. Postoperative complications after primary adult optical penetrating keratoplasty: Prevalence and impact on graft survival. Cornea 2009;28:385–94. 43. Bachmann B, Taylor RS, Cursiefen C. Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: an evidence-based meta-analysis. Ophthalmology 2010;117:1300–5.
Footnotes and Financial Disclosures Originally received: June 17, 2014. Final revision: September 20, 2014. Accepted: September 28, 2014. Available online: November 13, 2014.
The authors have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2014-951.
The Helsinki University Eye Hospital, University of Helsinki, Helsinki, Finland. Presented at: The 2014 World Ophthalmology Congress, Tokyo, Japan. Financial Disclosure(s): The Finnish Eye Foundation, the Evald and Hilda Nissi Foundation, the Finnish Ophthalmological Society and the Finnish Eye and Tissue Bank Foundation, Helsinki, Finland. The funding organizations had no role in the design or conduct of this research.
Abbreviations and Acronyms: BCVA ¼ best-corrected visual acuity; FAF ¼ familial amyloidosis, Finnish type; IOL ¼ intraocular lens; logMAR ¼ logarithm of the minimum angle of resolution; PK ¼ penetrating keratoplasty. Correspondence: Juha M. Holopainen, MD, PhD, Helsinki Eye Lab, Department of Ophthalmology, Helsinki University Eye Hospital, Haartmaninkatu 4 C, 00290 Helsinki, Finland. E-mail: juha.holopainen@hus.fi.
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