The challenging management of pediatric corneal transplantation: an overview of surgical and clinical experiences
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Abstract
Purpose
Pediatric keratoplasty is an immense challenge because of the technical complexity of the procedure and the high risk of rejection in young graft recipients. Our aim is to describe the major indications and appropriate timing of corneal transplantation intervention, including a report of our experience and surgical tips, in conjunction with the current literature.
Methods
Review of the literature on indications for keratoplasty in pediatric patients classified as: congenital, traumatic and acquired non-traumatic opacities. We additionally explored the challenges corneal surgeons face in performing this type of surgery and review the most pressing transplant-related problems and their management.
Results
Outcomes after pediatric keratoplasty, in terms of visual development, restoration and clarity of the graft, are influenced by peri-operative local and systemic conditions and factors, and by intraoperative management of the transplantation procedure itself.
Conclusion
Pediatric corneal transplantation is a critical tool for visual restoration and development in young patients with corneal opacities, particularly during the critical period of visual development. Successful management of the significant challenges associated with pediatric keratoplasty requires customized clinical and surgical management of each patient with particular attention paid to proper post-operative rehabilitation.
Keywords
Corneal transplantation Pediatric Congenital disease Peter’s anomalyNotes
Conflicts of interest
A. Di Zazzo, None; S. Bonini, None; S. Crugliano, None; M. Fortunato, None.
References
- 1.Waring GO 3rd, Laibson PR. Keratoplasty in infants and children. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1977;83:283–96.PubMedGoogle Scholar
- 2.Aasuri MK, Garg P, Gokhle N, Gupta S. Penetrating keratoplasty in children. Cornea. 2000;19:140–4.CrossRefPubMedGoogle Scholar
- 3.Beauchamp GR. Pediatric keratoplasty: problems in management. J Pediatr Ophthalmol Strabismus. 1979;16:388–94.PubMedGoogle Scholar
- 4.Al-Ghamdi A, Al-Rajhi A, Wagoner MD. Primary pediatric keratoplasty: indications, graft survival, and visual outcome. J AAPOS. 2007;11:41–7.CrossRefPubMedGoogle Scholar
- 5.Stulting RD, Sumers KD, Cavanagh HD, Waring GO 3rd, Gammon JA. Penetrating keratoplasty in children. Ophthalmology. 1984;91:1222–30.CrossRefPubMedGoogle Scholar
- 6.Dana MR, Moyes AL, Gomes JA, Rosheim KM, Schaumberg DA, Laibson PR, et al. The indications for and outcome in pediatric keratoplasty. A multicenter study. Ophthalmology. 1995;102:1129–38.CrossRefPubMedGoogle Scholar
- 7.Cowden JW. Penetrating keratoplasty in infants and children. Ophthalmology. 1990;97:324–8 (discussion 8–9).CrossRefPubMedGoogle Scholar
- 8.Huang SC, Soong HK, Brenz RM, Meyer RF, Sugar A. Problems associated with penetrating keratoplasty for corneal edema in congenital glaucoma. Ophthalmic Surg. 1989;20:399–402.PubMedGoogle Scholar
- 9.Huang C, O’Hara M, Mannis MJ. Primary pediatric keratoplasty: indications and outcomes. Cornea. 2009;28:1003–8.CrossRefPubMedGoogle Scholar
- 10.Vanathi M, Panda A, Vengayil S, Chaudhuri Z, Dada T. Pediatric keratoplasty. Surv Ophthalmol. 2009;54:245–71.CrossRefPubMedGoogle Scholar
- 11.Wiesel TN. Postnatal development of the visual cortex and the influence of environment. Nature. 1982;299:583–91.CrossRefPubMedGoogle Scholar
- 12.Rezende RA, Uchoa UB, Uchoa R, Rapuano CJ, Laibson PR, Cohen EJ. Congenital corneal opacities in a cornea referral practice. Cornea. 2004;23:565–70.CrossRefPubMedGoogle Scholar
- 13.Uyama S. Congenital anomalies of the cornea. Nihon ganka kiyo. 1964;15:134–40 (in Japanese).PubMedGoogle Scholar
- 14.Sharma N, Prakash G, Titiyal JS, Tandon R, Vajpayee RB. Pediatric keratoplasty in India: indications and outcomes. Cornea. 2007;26:810–3.CrossRefPubMedGoogle Scholar
- 15.Dana MR, Schaumberg DA, Moyes AL, Gomes JA, Laibson PR, Holland EJ, et al. Outcome of penetrating keratoplasty after ocular trauma in children. Arch Ophthalmol. 1995;113:1503–7.CrossRefPubMedGoogle Scholar
- 16.Wilson SE, McDonald MB, Kaufman HE. Bilateral penetrating keratoplasty in infants. Ophthalmic Surg. 1989;20:523–4.PubMedGoogle Scholar
- 17.Mullaney PB, Risco JM, Teichmann K, Millar L. Congenital hereditary endothelial dystrophy associated with glaucoma. Ophthalmology. 1995;102:186–92.CrossRefPubMedGoogle Scholar
- 18.Frucht-Pery J, Feldman ST, Brown SI. Transplantation of congenitally opaque corneas from eyes with exaggerated buphthalmos. Am J Ophthalmol. 1989;107:655–8.CrossRefPubMedGoogle Scholar
- 19.Astle WF, Lin DT, Douglas GR. Bilateral penetrating keratoplasty and placement of a Molteno implant in a newborn with Peters’ anomaly. Can J Ophthalmol. 1993;28:276–82.PubMedGoogle Scholar
- 20.Ariyasu RG, Silverman J, Irvine JA. Penetrating keratoplasty in infants with congenital glaucoma. Cornea. 1994;13:521–6.CrossRefPubMedGoogle Scholar
- 21.Erlich CM, Rootman DS, Morin JD. Corneal transplantation in infants, children and young adults: experience of the Toronto Hospital for Sick Children, 1979–88. Can J Ophthalmol. 1991;26:206–10.PubMedGoogle Scholar
- 22.Kirkness CM. The corneal endothelial dystrophies. Ann Acad Med Singapore. 1989;18:158–64.PubMedGoogle Scholar
- 23.Ehlers N, Modis L, Moller-Pedersen T. A morphological and functional study of Congenital Hereditary Endothelial Dystrophy. Acta Ophthalmol Scand. 1998;76:314–8.CrossRefPubMedGoogle Scholar
- 24.Waring GO 3rd, Rodrigues MM, Laibson PR. Corneal dystrophies. II. Endothelial dystrophies. Surv Ophthalmol. 1978;23:147–68.CrossRefPubMedGoogle Scholar
- 25.Pearce WG, Tripathi RC, Morgan G. Congenital endothelial corneal dystrophy. Clinical, pathological, and genetic study. Br J Ophthalmol. 1969;53:577–91.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Stirling R, Pitts J, Galloway NR, Robson K, Newbury-Ecob R. Congenital hereditary endothelial dystrophy associated with nail hypoplasia. Br J Ophthalmol. 1994;78:77–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Schaumberg DA, Moyes AL, Gomes JA, Dana MR. Corneal transplantation in young children with congenital hereditary endothelial dystrophy. Multicenter Pediatric Keratoplasty Study. Am J Ophthalmol. 1999;127:373–8.CrossRefPubMedGoogle Scholar
- 28.Botelho PJ, Congdon NG, Handa JT, Akpek EK. Keratoprosthesis in high-risk pediatric corneal transplantation: first 2 cases. Arch Ophthalmol (Chicago Ill: 1960). 2006;124:1356–7.CrossRefGoogle Scholar
- 29.Cameron JA. Good visual result following early penetrating keratoplasty for Peters’ anomaly. J Pediatr Ophthalmol Strabismus. 1993;30:109–12.PubMedGoogle Scholar
- 30.Ramamurthy B, Sachdeva V, Mandal AK, Vemuganti GK, Garg P, Sangwan VS. Coexistent congenital hereditary endothelial dystrophy and congenital glaucoma. Cornea. 2007;26:647–9.CrossRefPubMedGoogle Scholar
- 31.Barsky D, Dunn SP. Hereditary sclerocornea. Henry Ford Hosp Med J. 1985;33:185–9.PubMedGoogle Scholar
- 32.Elliott JH, Feman SS, O’Day DM, Garber M. Hereditary sclerocornea. Arch Ophthalmol. 1985;103:676–9.CrossRefPubMedGoogle Scholar
- 33.Khan AO. Sclerocornea and cornea plana are distinct entities. Surv Ophthalmol. 2007;52:325 (author’s reply 6).CrossRefPubMedGoogle Scholar
- 34.Doane JF, Sajjadi H, Richardson WP. Bilateral penetrating keratoplasty for sclerocornea in an infant with monosomy 21. Case report and review of the literature. Cornea. 1994;13:454–8.CrossRefPubMedGoogle Scholar
- 35.Gregersen E. Keratoplasty in babies with sclerocornea. To do or not to do? Report of an unsuccessful case. Dev Ophthalmol. 1981;5:52.CrossRefPubMedGoogle Scholar
- 36.Dada T, Sharma N, Vajpayee RB. Indications for pediatric keratoplasty in India. Cornea. 1999;18:296–8.CrossRefPubMedGoogle Scholar
- 37.Stone DL, Kenyon KR, Green WR, Ryan SJ. Congenital central corneal leukoma (Peters’ anomaly). Am J Ophthalmol. 1976;81:173–93.CrossRefPubMedGoogle Scholar
- 38.Musch DC, Meyer RF. Risk of endothelial rejection after bilateral penetrating keratoplasty. Ophthalmology. 1989;96:1139–43.CrossRefPubMedGoogle Scholar
- 39.Völker-Dieben HJ, Kok-van Alphen CC, Lansbergen Q, Persijn GG. Different influences on corneal graft survival in 539 transplants. Acta Ophthalmol (Copenh). 1982;60:190–202.CrossRefGoogle Scholar
- 40.Sajjadi H, Javadi MA, Hemmati R, Mirdeghan A, Parvin M, Nassiri N. Results of penetrating keratoplasty in CHED. Congenital hereditary endothelial dystrophy. Cornea. 1995;14:18–25.CrossRefPubMedGoogle Scholar
- 41.Al-Torbak AA. Outcome of combined Ahmed glaucoma valve implant and penetrating keratoplasty in refractory congenital glaucoma with corneal opacity. Cornea. 2004;23:554–9.CrossRefPubMedGoogle Scholar
- 42.Al-Torbak A. Graft survival and glaucoma outcome after simultaneous penetrating keratoplasty and ahmed glaucoma valve implant. Cornea. 2003;22:194–7.CrossRefPubMedGoogle Scholar
- 43.Lowe MT, Keane MC, Coster DJ, Williams KA. The outcome of corneal transplantation in infants, children, and adolescents. Ophthalmology. 2011;118:492–7.CrossRefPubMedGoogle Scholar
- 44.Beauchamp GR. Anterior segment dysgenesis keratolenticular adhesion and aniridia. J Pediatr Ophthalmol Strabismus. 1980;17:55–8.PubMedGoogle Scholar
- 45.Schanzlin DJ, Goldberg DB, Brown SI. Hallermann–Streiff syndrome associated with sclerocornea, aniridia, and a chromosomal abnormality. Am J Ophthalmol. 1980;90:411–5.CrossRefPubMedGoogle Scholar
- 46.Vajpayee RB, Vanathi M, Tandon R, Sharma N, Titiyal JS. Keratoplasty for keratomalacia in preschool children. Br J Ophthalmol. 2003;87:538–42.CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Vanathi M, Sharma N, Titiyal JS, Tandon R, Vajpayee RB. Tectonic grafts for corneal thinning and perforations. Cornea. 2002;21:792–7.CrossRefPubMedGoogle Scholar
- 48.Meiser S, Sundmacher R, Greber H. Keratoplasty in infancy and early childhood with special reference to the auto-rotation technique. Fortschr Ophthalmol. 1991;88:363–7 (in German).PubMedGoogle Scholar
- 49.Dana MR, Schaumberg DA, Moyes AL, Gomes JA. Corneal transplantation in children with Peters anomaly and mesenchymal dysgenesis. Multicenter Pediatric Keratoplasty Study. Ophthalmology. 1997;104:1580–6.CrossRefPubMedGoogle Scholar
- 50.McCartney DL, Gottsch JD, Stark WJ. Managing posterior pressure during pseudophakic keratoplasty. Arch Ophthalmol. 1989;107:1384–6.CrossRefPubMedGoogle Scholar
- 51.Casey TA. Penetrating keratoplasty in aphakia. Int Ophthalmol Clin. 1962;2:801–8.CrossRefPubMedGoogle Scholar
- 52.Fine M. Penetrating keratoplasty in aphakia. Arch Ophthalmol. 1964;72:50–6.CrossRefPubMedGoogle Scholar
- 53.Shimomura Y, Hosotani H, Kiritoshi A, Watanabe H, Tano Y. Core vitrectomy preceding triple corneal procedure in patients at high risk for increased posterior chamber pressure. Jpn J Ophthalmol. 1997;41:251–4.CrossRefPubMedGoogle Scholar
- 54.Forstot SL, Binder PS, Fitzgerald C, Kaufman HE. The incidence of retinal detachment after penetrating keratoplasty. Am J Ophthalmol. 1975;80:102–5.CrossRefPubMedGoogle Scholar
- 55.Li J, Dong XG. Black diaphragm intraocular lens implantation and penetrating keratoplasty in aphakic eyes with traumatic aniridia. Int J Ophthalmol. 2013;6:183–6.PubMedPubMedCentralGoogle Scholar
- 56.Kim YW, Choi HJ, Kim MK, Wee WR, Yu YS, Oh JY. Clinical outcome of penetrating keratoplasty in patients 5 years or younger: peters anomaly versus sclerocornea. Cornea. 2013;32:1432–6.CrossRefPubMedGoogle Scholar
- 57.Toker E, Seitz B, Langenbucher A, Dietrich T, Naumann GO. Penetrating keratoplasty for endothelial decompensation in eyes with buphthalmos. Cornea. 2003;22:198–204.CrossRefPubMedGoogle Scholar
- 58.Vajpayee RB, Ramu M, Panda A, Sharma N, Tabin GC, Anand JR. Oversized grafts in children. Ophthalmology. 1999;106:829–32.CrossRefPubMedGoogle Scholar
- 59.Yang LL, Lambert SR, Drews-Botsch C, Stulting RD. Long-term visual outcome of penetrating keratoplasty in infants and children with Peters anomaly. J AAPOS. 2009;13:175–80.CrossRefPubMedGoogle Scholar
- 60.Ashar JN, Pahuja S, Ramappa M, Vaddavalli PK, Chaurasia S, Garg P. Deep anterior lamellar keratoplasty in children. Am J Ophthalmol. 2013;155(570–4):e1.Google Scholar
- 61.Madi S, Santorum P, Busin M. Descemet stripping automated endothelial keratoplasty in pediatric age group. Saudi J Ophthalmol. 2012;26:309–13.CrossRefPubMedPubMedCentralGoogle Scholar
- 62.Ramappa M, Ashar J, Vaddavalli PK, Chaurasia S, Murthy SI. Endothelial keratoplasty in children: surgical challenges and early outcomes. Br J Ophthalmol. 2012;96:1149–51.CrossRefPubMedGoogle Scholar
- 63.Pineda R 2nd, Jain V, Shome D, Hunter DC, Natarajan S. Descemet’s stripping endothelial keratoplasty: is it an option for congenital hereditary endothelial dystrophy? Int Ophthalmol. 2010;30:307–10.CrossRefPubMedGoogle Scholar
- 64.Ramappa M, Bhalekar S, Chaurasia S, Mulay K, Trivedi RH, Wilson ME. Presumed allograft stromal rejection after deep anterior lamellar keratoplasty in a boy presenting with interface fluid syndrome. J AAPOS. 2013;17:554–7.CrossRefPubMedGoogle Scholar
- 65.Kawashima M, Mochizuki H, Kawakita T, Hatoh S, Shimazaki J, Yamada M. Presumed stromal graft rejection after automated lamellar therapeutic keratoplasty: case report. J Med Case Rep. 2007;1:10.CrossRefPubMedPubMedCentralGoogle Scholar
- 66.Melles GR, Remeijer L, Geerards AJ, Beekhuis WH. A quick surgical technique for deep, anterior lamellar keratoplasty using visco-dissection. Cornea. 2000;19:427–32.CrossRefPubMedGoogle Scholar
- 67.Harding SA, Nischal KK, Upponi-Patil A, Fowler DJ. Indications and outcomes of deep anterior lamellar keratoplasty in children. Ophthalmology. 2010;117:2191–5.CrossRefPubMedGoogle Scholar
- 68.Laver NM, Friedlander MH, McLean IW. Mild form of Maroteaux–Lamy syndrome: corneal histopathology and ultrastructure. Cornea. 1998;17:664–8.CrossRefPubMedGoogle Scholar
- 69.Lavery MA, Green WR, Jabs EW, Luckenbach MW, Cox JL. Ocular histopathology and ultrastructure of Sanfilippo’s syndrome, type III-B. Arch Ophthalmol. 1983;101:1263–74.CrossRefPubMedGoogle Scholar
- 70.Kawashima M, Kawakita T, Den S, Shimmura S, Tsubota K, Shimazaki J. Comparison of deep lamellar keratoplasty and penetrating keratoplasty for lattice and macular corneal dystrophies. Am J Ophthalmol. 2006;142:304–9.CrossRefPubMedGoogle Scholar
- 71.Basu S, Sangwan VS. Pediatric lamellar keratoplasty. Ophthalmology. 2011;118:1900–1 (author reply 1–2).CrossRefPubMedGoogle Scholar
- 72.Anwar M, Teichmann KD. Big-bubble technique to bare Descemet’s membrane in anterior lamellar keratoplasty. J Cataract Refract Surg. 2002;28:398–403.CrossRefPubMedGoogle Scholar
- 73.Buzzonetti L, Petrocelli G, Valente P. Big-bubble deep anterior lamellar keratoplasty assisted by femtosecond laser in children. Cornea. 2012;31:1083–6.CrossRefPubMedGoogle Scholar
- 74.Chaurasia S, Ramappa M, Murthy SI, Garg P, Sangwan VS. Endothelial keratoplasty without stripping the Descemet’s membrane. Br J Ophthalmol. 2011;95:1473–4.CrossRefPubMedGoogle Scholar
- 75.Price FW Jr, Price MO. Endothelial keratoplasty to restore clarity to a failed penetrating graft. Cornea. 2006;25:895–9.CrossRefPubMedGoogle Scholar
- 76.Lee WB, Jacobs DS, Musch DC, Kaufman SC, Reinhart WJ, Shtein RM. Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology. Ophthalmology. 2009;116:1818–30.CrossRefPubMedGoogle Scholar
- 77.Ponchel C, Malecaze F, Arne JL, Fournie P. Descemet stripping automated endothelial keratoplasty in a child with descemet membrane breaks after forceps delivery. Cornea. 2009;28:338–41.CrossRefPubMedGoogle Scholar
- 78.Busin M, Beltz J, Scorcia V. Descemet-stripping automated endothelial keratoplasty for congenital hereditary endothelial dystrophy. Arch Ophthalmol. 2011;129:1140–6.CrossRefPubMedGoogle Scholar
- 79.Ashar JN, Madhavi Latha K, Vaddavalli PK. Descemet’s stripping endothelial keratoplasty (DSEK) for children with congenital hereditary endothelial dystrophy: surgical challenges and 1-year outcomes. Graefes Arch Clin Exp Ophthalmol. 2012;250:1341–5.CrossRefPubMedGoogle Scholar
- 80.Ashar JN, Ramappa M, Chaurasia S. Endothelial keratoplasty without Descemet’s stripping in congenital hereditary endothelial dystrophy. J AAPOS. 2013;17:22–4.CrossRefPubMedGoogle Scholar
- 81.Vajpayee RB, Ray M, Panda A, Sharma N, Taylor HR, Murthy GV, et al. Risk factors for pediatric presumed microbial keratitis: a case-control study. Cornea. 1999;18:565–9.CrossRefPubMedGoogle Scholar
- 82.Alldredge OC, Krachmer JH. Clinical types of corneal transplant rejection. Their manifestations, frequency, preoperative correlates, and treatment. Arch Ophthalmol. 1981;99:599–604.CrossRefPubMedGoogle Scholar
- 83.Comer RM, Daya SM, O’Keefe M. Penetrating keratoplasty in infants. J AAPOS. 2001;5:285–90.CrossRefPubMedGoogle Scholar
- 84.Kusumesh R, Vanathi M. Graft rejection in pediatric penetrating keratoplasty: clinical features and outcomes. Oman J Ophthalmol. 2015;8:33–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 85.Cosar CB, Laibson PR, Cohen EJ, Rapuano CJ. Topical cyclosporine in pediatric keratoplasty. Eye Contact Lens. 2003;29:103–7.CrossRefPubMedGoogle Scholar
- 86.Von Noorden GK. Classification of amblyopia. Am J Ophthalmol. 1967;63:238–44.CrossRefGoogle Scholar
- 87.Steele A. Pediatric ophthalmology and strabismus. In: Taylor D, Hoyt CS, editors. 3rd ed. Elsevier Ltd.; 2005. p. 167.Google Scholar
- 88.Keech RV, Kutschke PJ. Upper age limit for the development of amblyopia. J Pediatr Ophthalmol Strabismus. 1995;32:89–93.PubMedGoogle Scholar
- 89.Zaidman G, Ramirez T, Kaufman A, Palay D, Phillips R, Medow N. Successful surgical rehabilitation of children with traumatic corneal laceration and cataract. Ophthalmology. 2001;108:338–42.CrossRefPubMedGoogle Scholar
- 90.Zacharia PT, Harrison DA, Wheeler DT. Penetrating keratoplasty with a valved glaucoma drainage implant for congenital glaucoma and corneal scarring secondary to hydrops. Ophthalmic Surg Lasers. 1998;29:318–22.PubMedGoogle Scholar
- 91.Al-Rajhi AA, Wagoner MD. Penetrating keratoplasty in congenital hereditary endothelial dystrophy. Ophthalmology. 1997;104:956–61.CrossRefPubMedGoogle Scholar
- 92.Javadi MA, Baradaran-Rafii AR, Zamani M, Karimian F, Zare M, Einollahi B, et al. Penetrating keratoplasty in young children with congenital hereditary endothelial dystrophy. Cornea. 2003;22:420–3.CrossRefPubMedGoogle Scholar
- 93.Wagoner MD, Al-Ghamdi AH, Al-Rajhi AA. Bacterial keratitis after primary pediatric penetrating keratoplasty. Am J Ophthalmol. 2007;143:1045–7.CrossRefPubMedGoogle Scholar
- 94.Vanathi M, Sharma N, Sinha R, Tandon R, Titiyal JS, Vajpayee RB. Indications and outcome of repeat penetrating keratoplasty in India. BMC Ophthalmol. 2005;5:26.CrossRefPubMedPubMedCentralGoogle Scholar
- 95.Yang LL, Lambert SR, Lynn MJ, Stulting RD. Long-term results of corneal graft survival in infants and children with peters anomaly. Ophthalmology. 1999;106:833–48.CrossRefPubMedGoogle Scholar
- 96.Aldave AJ, Rudd JC, Cohen EJ, Rapuano CJ, Laibson PR. The role of glaucoma therapy in the need for repeat penetrating keratoplasty. Cornea. 2000;19:772–6.CrossRefPubMedGoogle Scholar
- 97.Kenyon KR. Mesenchymal dysgenesis in Peter’s anomaly, sclerocornea and congenital endothelial dystrophy. Exp Eye Res. 1975;21:125–42.CrossRefPubMedGoogle Scholar
- 98.Aquavella JV. Pediatric keratoprosthesis: a new surgical approach. Ann Ophthalmol. 2008;40:64–7.Google Scholar
- 99.Zingirian M. Keratoplasty for sclerocornea in early infancy. Fortschritte der Ophthalmologie: Fortschr Ophthalmol. 1987;84:429–31.PubMedGoogle Scholar
- 100.Parmley VC, Stonecipher KG, Rowsey JJ. Peters’ anomaly: a review of 26 penetrating keratoplasties in infants. Ophthalmic Surg. 1993;24:31–5.PubMedGoogle Scholar
- 101.Williams KA, Roder D, Esterman A, Muehlberg SM, Coster DJ. Factors predictive of corneal graft survival. Report from the Australian Corneal Graft Registry. Ophthalmology. 1992;99:403–14.CrossRefPubMedGoogle Scholar