Long-Term Clinical Course in Eyes with Peters Anomaly

CLINICAL SCIENCE

Long-Term Clinical Course in Eyes With Peters Anomaly

Haruna Yoshikawa, MD,* Chie Sotozono, MD, PhD,* Yoko Ikeda, MD, PhD,* Kazuhiko Mori, MD, PhD,* Morio Ueno, MD, PhD,* and Shigeru Kinoshita, MD, PhD†

size and density surrounded by a relatively clear peripheral Purpose: Peters anomaly (PA) is known to be a primary cause of cornea.3 In 50% to 80% of PA cases, the affliction is bilateral. PA congenital corneal opacity. The aim of this study is to report the is classified as one of the developmental anomalies of the anterior long-term clinical course and visual achievement of patients with PA segment, and glaucoma is reportedly present in 50% to 70% of who did not undergo keratoplasty. the cases.4,5 In a study conducted by our group,6 ultrasound fi Methods: This retrospective study involved 15 eyes of 9 infants with biomicroscopy ndings showed that PA and sclerocornea exhibit PA less than 5 months of age at initial presentation at the Kyoto a similar-looking absence of Descemet membrane and iridocor- Prefectural University of Medicine who were followed up without neal synechiae at the edge of opacity, thus indicating that both keratoplasty for more than 6 years after presentation. In each subject, diseases fall into the same disease category, that is, they are both visual acuity, intraocular pressure (IOP), presence of congenital glau- developmental anomalies of the anterior segment. coma, and change of corneal opacity were retrospectively investigated. It is well known that severe corneal opacity from birth greatly interferes with the development of vision, and penetrating Results: At initial presentation, the mean patient age was 2.3 keratoplasty (PKP) is currently the only available surgical method months (SD: 1.3; range: 0–4 mo), and the mean follow-up period to obtain a clear cornea. However, PKP is more difficult to was 7.9 years (SD: 1.8; range: 6.5–11.3 yrs). Of the 9 patients, 6 perform in infants than in adults because of the elasticity of the were affected bilaterally. Thirteen eyes of 7 patients were found to host cornea, scleral collapse, and anterior movement of the lens have glaucoma. Over the follow-up period, corneal opacity gradually even when a scleral ring is used.7 In addition, the prognosis of decreased in 4 eyes, 1 eye each of 2 unilateral patients without PKP for children is poor, especially in infants, as the rate of graft glaucoma and both eyes of 1 bilaterally affected patient with good rejection is high and secondary glaucoma due to corticosteroids IOP control during the follow-up period. Visual acuity in the and/or associated anterior segment abnormalities can easily occur. unilateral case with intensive amblyopia treatment gradually Numerous studies have investigated the rate of graft increased along with decreasing corneal opacity. survival and long-term prognosis in infants and children with PA8–12; however, the long-term course of corneal opacity and fi Conclusions: The ndings of this study show that a natural visual achievement in those who do not undergo keratoplasty decrease of corneal opacity can occur in eyes with PA. In cases of are unclear. Thus, the purpose of this retrospective study was unilateral PA without IOP elevation and no enlargement of the to examine the long-term clinical course in patients with PA corneal diameter, strict amblyopia treatment is vital to obtain seen at the Kyoto Prefectural University of Medicine, Kyoto, a favorable visual prognosis. Japan, who did not undergo keratoplasty. Key Words: Peters anomaly, congenital corneal opacity, transparency, glaucoma METHODS – (Cornea 2017;36:448 451) This study was approved by the institutional review boards of Kyoto Prefectural University of Medicine (KPUM). All experimental procedures were conducted in accordance ongenital corneal opacity is a rare but serious vision- with the principles of the Helsinki Declaration. Cthreatening disease. The reported incidence of congenital corneal opacity is 2 to 3 cases in every 100,000 births.1,2 The primary cause of congenital corneal opacity is Peters anomaly Patients (PA), which is characterized by central corneal opacity of variable This retrospective study involved patients with PA seen Received for publication September 30, 2016; revision received December at the Department of Ophthalmology, Kyoto Prefectural 20, 2016; accepted December 21, 2016. Published online ahead of print University of Medicine, between September 1, 2001, and February 15, 2017. August 6, 2016, who were less than 5 months of age at the time † From the Departments of *Ophthalmology; and Frontier Medical Science and of initial presentation, who did not undergo keratoplasty, and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. who were followed up for more than 6 years after presentation. The authors have no funding or conflicts of interest to disclose. Reprints: Haruna Yoshikawa, MD, Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Hirokoji-agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto 602-0841, Japan (e-mail: Clinical Diagnosis of PA [email protected]). In all patients, the diagnosis of PA was confirmed based Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. on slit-lamp appearance and ultrasound biomicroscopy

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Copyright Ó 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Cornea Volume 36, Number 4, April 2017 Long-Term Clinical Course in Peters Anomaly Eyes

findings except 2 cases. PA was characterized by central bilateral corneal opacity and 3 had unilateral corneal opacity. corneal opacity, thin stromal thickness at the center of the In all cases, the optic disc of the affected eye could not be cornea, a clear peripheral cornea, and iridocorneal synechiae. seen at initial examination because of corneal opacity. At Eyes with a history of infection or trauma were excluded from initial examination, mean patient age was 2.3 months (SD: the study. All cased were classified as type 1 (the milder form 1.3; range: 0–4 mo). The mean follow-up period was 7.9 that does not involve cataracts) or type 2 (the more severe years (SD: 1.8; range: 6.5–11.3 yrs), and the mean patient age form that involves cataracts), and whether the case included at final follow-up was 8.2 years (SD: 1.7; range: 6–11 yrs). disease and/or some systemic involvement. During the follow-up periods, 13 eyes of 7 cases (86.7%) were diagnosed with glaucoma (cases 1 through 7 in Tables 1 Diagnosis of Glaucoma and 2) and 5 of those eyes required glaucoma surgery. Goldman perimetry examination was performed in 2 patients, In all subjects, intraocular pressure (IOP) was measured and none of the patients showed visual field constriction. with a Perkins applanation tonometer (Haag Streit USA, Mason, Corneal opacity gradually decreased in 4 eyes of 3 OH), an Icare tonometer (Finland Oy, Helsinki, Finland), patients (4 of the 15 eyes: 26.5%) (Fig. 1 and Table 2); noncontact tonometer (Nidek Co, Ltd, Gamagori, Japan), and/or that is, a year-by-year increase of corneal transparency a Tono-Pen XL (Medtronic Solan, Jacksonville, FL) tonometer. was obtained in those 4 eyes. Of those 4 eyes, 2 were Tactile examination was also performed. Eyes accompanied unilateral and not accompanied with glaucoma and 2 were with elevated IOP and/or enlargement of the corneal diameter both eyes of one patient accompanied with glaucoma; were diagnosed with glaucoma. however, no enlargement of the cornea was observed and IOP was well controlled during the follow-up periods. RESULTS These 4 eyes were considered to be the less-severe type of PA. Patient Characteristics Visual acuity (VA) could be examined in 15 eyes of the This study involved 15 eyes of 9 infants (6 males and 3 9 patients. In 8 of those eyes, VA was greater than 0.01, yet in females) with corneal opacity. Of those 9 patients, 6 had 7 eyes it was less than 0.01. VA in 4 eyes of the 3 cases with

TABLE 1. Patient Characteristics at Initial Presentation Ocular IOP, Cornea Diameter No. Complication Affected mm (Vertical · Antiglaucoma Except for Systemic Case No. Sex Eye Age Hg Horizontal, mm) Eye Drops Glaucoma Complication Cataract Type of PA Bilateral 1 Female R 4 mo (25)p 13.5 · 13.5 1 Aniridia Hydronephrosis, atrial 2 Type 1, plus septal defect disease L (27)p 14 · 13 1 Aniridia 2 2 Male R 3 mo 34p 11 · 10.5 2 ——2 Type 1 L34p 14 · 15.5 2 Entropion, — 2 buphthalmos, aniridia 3 Male R 8 d 40p 13 · 13 0 — Ventricular septal 2 Type 1, plus L26p 14 · 14 0 — defect, pulmonary 2 disease atresia 4 Male R 4 mo (23)i No data 1 ——2 Type 1 L (24)i No data 1 ——2 5 Male R 2 mo (24)i No data 0 ——2 Type 1 L (24)i No data 0 — 2 6 Female R 2 mo 19i 6 · 7 0 Esotropia — 2 Type 1 L23i 6 · 80 — 2 Unilateral 7 Female L 3 mo 25p 10 · 10 2 ——2 Type 1 8 Male R 1 mo 17i No data 0 Cataract, esotropia Bronchial asthma, + Type 2, plus cryptorchidism, disease developmental delay, deafness 9 Male L 2 mo (6)i No data 0 Exotropia, — 2 Type 1 microphthalmia

Cases 1 through 7: accompanied with glaucoma, cases 8 and 9: no glaucoma. Only case 8 had involvement crystalline lens. R, right eye; L, left eye; IOP, intraocular pressure at initial presentation; ( ), IOP measured after Initial Presentation; p, Perkins applanation tonometer; i, Icare tonometer; mo, months; d, days.

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TABLE 2. Patient Characteristics at Final Follow-up Number of Number of Antiglaucoma Case No. Affected Eye Age, yrs VA IOP, mm Hg Glaucoma Operations Eye Drops Corneal Clarity Bilateral 1 R 11 0.03 15g 2 0 No change LCF39g 3 3 No change 2 R 8 0.01 15g 0 1 No change LHM13g 1 2 No change 3 R 11 HM 16g 3 3 No change L 0.02 14g 2 3 No change 4R8HM19i 0 1 No change LCF15i 0 1 No change 5 R 7 0.6 24n 0 1 Improved L 0.08 24n 0 1 Improved 6 R 8 0.05 20g 0 3 Slightly improved L 0.08 16g 0 3 Slightly improved Unilateral 7L8HM17g 0 0 No change 8R7CF18i 0 0 Improved 9 L 6 0.3 21i 0 0 Improved

Cases 1 through 7: accompanied with glaucoma, cases 8 through 9: no glaucoma. R, right eye; L, left eye; CF, counting fingers; HM, hand motion; IOP, intraocular pressure at final follow-up; g, Goldmann applanation tonometer; i, Icare tonometer; n, noncontact tonometer. the increase in corneal transparency was 0.6, 0.08, counting did not change in those eyes. It is noteworthy that of the PA fingers, and 0.3 (Table 2). cases in this study that achieved improved corneal transparency, 2 eyes were unilaterally affected and had no glaucoma. DISCUSSION In a previous study, Sano et al13 reported that in 34 eyes The results of this study revealed that a natural decrease of 24 cases with PA, corneal opacity decreased in 14 eyes of corneal opacity can be expected in eyes with PA. In this without corneolenticular approximation yet increased in 4 study, 13 eyes of 7 of the 9 infants with PA were eyes, which were associated with glaucoma. In a report by accompanied with glaucoma. Even after obtaining normal Ohkoshi et al,14 the authors showed that corneal opacity had IOP through medication or glaucoma surgery, corneal opacity gradually decreased in 9 of 10 eyes with PA; that is, in 1 eye

FIGURE 1. Anterior photographs showing the change of corneal opacity in 2 infants with PA. A and B, Anterior photographs of the right eye of case 1. A, Corneal opacity at the age of 2 years and 4 months. B, Corneal opacity at the age of 9 years and 3 months. No decrease of corneal opacity can be seen. C and D, Anterior photographs of the left eye of case 9. C, Corneal opacity at the age of 2 months. D, Corneal opacity at the age of 4 years. A substantial decrease of corneal opacity can be seen.

Copyright Ó 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Cornea Volume 36, Number 4, April 2017 Long-Term Clinical Course in Peters Anomaly Eyes accompanied by only a central posterior corneal defect and in ACKNOWLEDGMENTS 8 eyes with central iridocorneal adhesion. Considering the The authors wish to thank John Bush for reviewing results of those previous reports and our study, it is highly the article. likely that in eyes with the less-severe type of PA, yet without glaucoma, corneal opacity can be expected to decrease during REFERENCES the first several years from birth. 1. Kurilec JM, Zaidman GW. Incidence of Peters anomaly and congenital In cases in which PA is unilateral, there is a need for corneal opacities interfering with vision in the United States. Cornea. – amblyopia treatment from an early stage. In case 9 in this 2014;33:848 850. fi 2. Bermejo E, Martínez-Frías ML. Congenital eye malformations: clinical- study, we began strict amblyopia therapy from the rst epidemiological analysis of 1,124,654 consecutive births in Spain. Am J appearance, and at age 5, corneal topography imaging Med Genet. 1998;75:497–504. revealed the presence of irregular astigmatism. Thus, we 3. Shigeyasu C, Yamada M, Mizuno Y, et al. Clinical features of anterior prescribed a rigid-type contact lens for correction of segment dysgenesis associated with congenital corneal opacities. Cornea. 2012;31:293–298. astigmatism and continued the occlusion of the healthy 4. Rubin SE, Marcus CH. Glaucoma in childhood. Ophthalmol Clin North contralateral eye. Thereafter, the patient’s VA improved. Am. 1996;9:215–227. Hence, it is key to start amblyopia therapy as early as 5. Stone DL, Kenyon KR, Green WR, et al. Congenital central corneal possible and to continue the treatment throughout the leukoma (Peters’ anomaly). Am J Ophthalmol. 1976;81:173–193. 6. Yoshikawa H, Ikeda Y, Sotozono C, et al. Ultrasound biomicroscopy in follow-up period. infants with congenital corneal opacity and its correlations with clinical Reportedly, postoperative complications such as graft diagnosis and intraocular pressure. Nihon Ganka Gakkai Zasshi. 2015; failure, cataract, inoperable retinal detachment, and phthisis 119:16–21. occur more frequently in infants and children than in 7. Townsend WM. Congenital anomalies of the cornea. In: Kaufman HE, 9,10 ed. The Cornea. New York, NY; Edinburgh, Scotland; London, United adults. One therapy option is to carefully observe corneal Kingdom; Melbourne, Australia: Churchill Livingstone; 1998:355. transparency while applying amblyopia treatment. Because 8. Chang JW, Kim MK, Kim JH, et al. Long-term visual outcomes of this retrospective study involved only a small number of penetrating keratoplasty for Peters anomaly. Graefes Arch Clin Exp cases, further prospective investigations involving a larger Ophthalmol. 2013;251:953–958. patient cohort are needed. 9. Yang LL, Lambert SR, Drews-Botsch C, et al. Long-term visual outcome fi of penetrating keratoplasty in infants and children with Peters anomaly. In summary, the ndings of this study demonstrated J AAPOS. 2009;13:175–180. that congenital corneal opacities decreased in 4 PA eyes 10. Yang LL, Lambert SR, Lynn MJ, et al. Long-term results of corneal graft during the first 6 years of observation. Two eyes were survival in infants and children with Peters anomaly. Ophthalmology. unilateral PA without glaucoma and 2 eyes of one case 1999;106:833–848. 11. Chang JW, Kim JH, Kim SJ, et al. Long-term clinical course and visual presented controlled IOP during the follow-up periods. In outcome associated with Peters’ anomaly. Eye (Lond). 2012;26:1237–1242. other words, our findings show that PA-associated corneal 12. Basdekidou C, Dureau P, Edelson C, et al. Should unilateral congenital opacity has the potential for spontaneous improvement corneal opacities in Peters’ anomaly be grafted? Eur J Ophthalmol. 2011; without surgical intervention. Thus, patient follow-up without 21:695–699. 13. Sano M, Ozeki H, Shirai S, et al. Clinical course of corneal opacity in surgical intervention is one option for treating PA. To obtain Peters’ anomaly. J Clin Ophthalmol. 1994;48:995–999. a favorable visual prognosis, strict amblyopia treatment 14. Ohkoshi K, Hayakawa M, Yamaguchi T, et al. A clinical study of 8 cases is vital. of Peters’ anomaly. Nihon Ganka Kiyou. 1989;40:909–914.