Clinical Manifestations of Congenital Aniridia

Home , Anil Kumar Mandal, Aniridia, Aphakia, Buphthalmos, Coloboma, Megalocornea

Bhupesh Singh, MD; Ashik Mohamed, MBBS, M Tech; Sunita Chaurasia, MD; Muralidhar Ramappa, MD; Anil Kumar Mandal, MD; Subhadra Jalali, MD; Virender S. Sangwan, MD

ABSTRACT

Purpose: To study the various clinical manifestations as- were subluxation, coloboma, posterior lenticonus, and sociated with congenital aniridia in an Indian population. microspherophakia. Corneal involvement of varying degrees was seen in 157 of 262 (59.9%) eyes, glaucoma Methods: In this retrospective, consecutive, observa- was identified in 95 of 262 (36.3%) eyes, and foveal hy- tional case series, all patients with the diagnosis of con- poplasia could be assessed in 230 of 262 (87.7%) eyes. genital aniridia seen at the institute from January 2005 Median age when glaucoma and cataract were noted to December 2010 were reviewed. In all patients, the was 7 and 14 years, respectively. None of the patients demographic profile, visual acuity, and associated sys- had Wilm’s tumor. temic and ocular manifestations were studied. Conclusions: Congenital aniridia was commonly as- Results: The study included 262 eyes of 131 patients sociated with classically described ocular features. with congenital aniridia. Median patient age at the time However, systemic associations were characteristically of initial visit was 8 years (range: 1 day to 73 years). Most absent in this population. Notably, cataract and glau- cases were sporadic and none of the patients had par- coma were seen at an early age. This warrants a careful ents afflicted with aniridia. The most common anterior evaluation and periodic follow-up in these patients for segment abnormality identified was lenticular changes. timely identification and appropriate management. Cataract was the predominant lens finding, observed in 93 of 231 (40.3%) phakic eyes. Other lens abnormalities [J Pediatr Ophthalmol Strabismus 20XX;XX:XX-XX.]

INTRODUCTION without systemic involvement, caused by mutation Congenital aniridia is a rare, panophthalmic of PAX6 or deletion of a regulatory region control- disorder affecting the iris, cornea, anterior chamber ling its expression, or as part of the Wilm’s tumor- angle, lens, retina, and optic nerve. Three variants aniridia-genital anomalies-retardation (WAGR) are described in the literature: autosomal domi- syndrome, with a deletion of 11p13 involving the nant, autosomal recessive, and sporadic. Aniridia PAX6 (aniridia) locus and adjacent WT1(Wilm’s may occur either as an isolated ocular abnormality tumor) locus.1-3

From Cornea and Anterior Segment Services (BS, SC, MR, VSS), Prof. Brien Holden Research Centre (AM), Anil Kumar Mandal, MD, is from VST Glaucoma Services (AKM), and Smt Kannuri Santhamma Centre for Vitreo-retinal Diseases (SJ), L. V. Prasad Eye Institute, Hyderabad, India. Submitted: April 7, 2013; Accepted: October 10, 2013; Posted online: January 3, 2014 The authors have no financial or proprietary interest in the materials presented herein. Correspondence: Sunita Chaurasia, MD, Cornea and Anterior Segment Services, L. V. Prasad Eye Institute, Kallam Anji Reddy Campus, L. V. Prasad Marg, Banjara Hills, Hyderabad -500 034, India. E-mail: [email protected] doi: 10.3928/01913913-20131223-01

Journal of Pediatric Ophthalmology & Strabismus • Vol. xx, No. x, 20XX 1 reported as median with interquartile range (IQR). TABLE 1 Comparison of the two independent groups was per- Demographic and Clinical Information formed using the independent t test (for parametric Characteristics Results data) and Mann–Whitney U test (for non-paramet- Age at first visit ric data). The chi-square test was used for univariate Median 8 years analysis of categorical variables. A P value of less than Interquartile range 8 months to 18 years .05 was considered statistically significant. Range 1 day to 73 years Gender RESULTS Demographic Data Male 67 (51.2%) Table 1 illustrates the demographic data. Median Female 64 (48.8%) age at the time of first visit to the hospital was 8 years Laterality (IQR: 8 months to 18 years; range: 1 day to 73 years). Bilateral 127 (97.0%) Fifteen patients (11.5%) were younger than 1 month. Unilateral 1 (0.7%) Sixty-seven were male (51.2%) and 64 (48.8%) were Could not be assessed 3a (2.3%) female. Of the 131 patients, 127 (96.9%) had bilat- Extent of aniridia eral aniridia and 1 had unilateral aniridia (the other eye being normal). In 3 patients, the fellow eye was Total eyes 220 (85.6%) phthisical at the time of presentation. Nine patients Partial eyes 37 (14.4%) had a positive familial history of aniridia, with one or a Three eyes were phthisical, hence evaluation was not possible. more affected siblings. However, none of the parents of these patients were noted to have aniridia. There Visual acuity may be affected due to various was no systemic disorder except for cyanotic heart associated ocular abnormalities. The classic ocular disease in one patient. Ultrasound of the abdomen manifestations in congenital aniridia include kera- revealed a normal study in all patients. topathy, glaucoma, cataract, lens subluxation, and foveal hypoplasia.4 The purpose of this study was to Visual Acuity investigate the various ocular and systemic features The median visual acuity at presentation was associated with congenital aniridia in Indian eyes. 1.00 logMAR unit (IQR: 0.78 to 1.40; range: 0.10 to 2.10). Visual acuity was hand motions in 56 eyes PATIENTS AND METHODS of 28 patients, light perception with accurate pro- The case records of patients identified with con- jection of light in 21 eyes, and no light perception in genital aniridia at our institution from November 8 eyes. Seventy-six (55.8%) patients had horizontal, 2005 to October 2010 were reviewed. Two hundred jerk nystagmus. sixty-two eyes of 131 patients were included and the charts were analyzed for the demographic profile, Ophthalmic Manifestations visual acuity, ocular features, systemic associations, Table 2 describes the ocular and extraocular and surgical interventions. Clinical examination features in congenital aniridia. Corneal involvement included a thorough evaluation of the anterior and was observed in 157 of 262 (59.9%) eyes. Corneal posterior segment, intraocular pressure assessment haze and vascularization of variable extent was seen using Goldmann’s/Perkin’s applanation tonometry, in 119 eyes, of which 29 (11.0%) eyes had clinical general examination, and ultrasound of the abdo- features suggestive of complete limbal stem cell de- men to rule out Wilm’s tumor. ficiency, characterized by 3,600 vascularization with Statistical analysis was done using Origin 7.0 conjunctivalization. Twenty-four eyes had megalo- (OriginLab Corporation, Northampton, MA) and cornea (corneal diameter > 12 mm) as a result of STATA 11.0 (StataCorp, College Station, TX). Sha- buphthalmos secondary to congenital glaucoma. piro–Wilk test was used to check for normality of Seven eyes had microcornea and 6 eyes were mi- distribution of continuous variables. Continuous crophthalmic. parametric data were reported as mean ± standard The lens status was phakic in 247 (94.3%) of deviation and continuous nonparametric data were the 262 eyes. The remaining eyes had previously

2 Copyright © SLACK Incorporated TABLE 2 Clinical Manifestations Clinical Features No. of Eyes (n = 262) Cornea Corneal opacification 119 (45.4%) Megalocornea 24 (9.2%) Microcornea 7 (2.7%) Lens Phakic 247 (94.3%) Clear lens 152 (61.5%) Cataract lens 95 (38.5%)

Pseudophakia 6 (2.3%) Figure 1. Box-whisker plot showing the age distribution of con- Surgical aphakia 9 (3.4%) genital aniridic eyes with and without glaucoma. Microspherophakia 6 (2.3%) Lens coloboma 6 (2.3%) 2 eyes. In 8 eyes, lens status could not be assessed because there was dense corneal scar. In these cases, Posterior lenticonus 2 (0.8%) presence of the lens was confirmed by B-scan ultra- Subluxation 55 (22.3%) sound. In 2 eyes, the lens was absorbed. Superior 45 (17.2%) Foveal hypoplasia was the most common pos- Superotemporal 6 (2.3%) terior segment finding, which could be assessed in Anterior dislocation 3 (1.2%) 230 (87.7%) eyes. Vitreous opacities were seen in Glaucoma 95 (36.3%) 15 (16.1%) eyes. Optic disc was pale in 13 eyes and Eyelids and adnexa hypoplastic in 7 eyes. Three eyes had a retinal de- Ptosis 6 (2.3%) tachment. Glaucoma was identified in 95 of 262 (36.3%) CNLDO 3 (1.2%) eyes. The median age at which glaucoma was doc- Ocular alignment umented in this population was 7 years (IQR: 23 Exotropia 12 (4.6%) days to 16 years; range: 1 day to 38 years). Twelve Posterior segment patients were exotropic, 3 had unilateral congenital Foveal hypoplasia 230 (87.7%) nasolacrimal duct obstruction, and 4 had unilateral Disc pallor 13 (5.0%) or bilateral congenital ptosis. Hypoplastic disc 7 (2.7%) The median age when cataract was noted was 14 years (IQR: 7 to 23 years; range: 1.5 months Vitreous opacities 15 (5.7%) to 54 years). The patients with concomitant glau- Retinal detachment 3 (1.1%) coma presented earlier than those without glaucoma CNLDO = congenital nasolacrimal duct obstruction (non-glaucoma median: 10 years; IQR: 1 to 18 years; range: 8 days to 73 years; P = .008). There was no gender preponderance in the presence of undergone lens surgery; 6 (2.3%) were pseudo- glaucoma (P = .89) and cataract (P = .21) in patients phakic and 9 (3.4%) were aphakic. The lens was with congenital aniridia. However, males (32.0%) cataractous in 95 of 247 (38.5%) phakic eyes. Lens had a higher proportion of associated subluxation subluxation was noted in 55 of 247 (22.3%) phakic (P = .001) compared to females (13.9%) (Figure 1). eyes (mean age: 11.9 ± 6.7 years, range: 1 month to 31 years). Of these, 46 eyes had superior sublux- DISCUSSION ation, 6 eyes had superotemporal subluxation, and 3 The prevalence of aniridia is 1:40,000 to eyes had anterior dislocation of lens. Other associ- 1:100,000. Isolated aniridia is inherited in an auto- ated lens features were microspherophakia in 6 eyes, somal dominant manner with almost complete pen- lens coloboma in 6 eyes, and posterior lenticonus in etrance and variable expressivities in two-thirds of

Journal of Pediatric Ophthalmology & Strabismus • Vol. xx, No. x, 20XX 3 cases; one-third of the cases are sporadic.4-6 In con- was noted in 87.7% of the eyes. The incidence of trast to existing reports, the pattern of inheritance glaucoma in cases of congenital aniridia has been was sporadic in the majority (93.3%) of patients in reported to range from 6% to 75%. In our series, our population. No gender preponderance was ob- 36.3% of eyes had glaucomatous disc changes. Oth- served in our population (male:female ratio = 1:1) er ocular abnormalities noted were microcornea or and none of the patients had the classic systemic as- megalocornea, hypoplastic disc, disc pallor, retinal sociations reported with congenital aniridia. detachment, ptosis, strabismus, and congenital na- Iris hypoplasia in congenital aniridia may be solacrimal duct obstruction. total or partial. The majority of patients (85.6%) Congenital aniridia can be associated with mul- in our study had total/complete aniridia. The com- tiple ocular abnormalities. Cataract and glaucoma mon ocular abnormalities associated with aniridia can develop at an early age. Emphasis is laid on that affect vision are cataract, glaucoma, corneal regular and careful ocular examinations to identify opacification and vascularization, and foveal hypo- these abnormalities for a timely and appropriate plasia. Corneal involvement often leads to decreased management of these patients. visual acuity because of aniridic keratopathy, which is due to ingrowths of blood vessels at the limbus REFERENCES and begins during the first decade of life.7 In this 1. Kokotas H, Petersen MB. Clinical and molecular aspects of aniridia. Clin Genet. 2010;77:409-420. series, 44.4% had varying degrees of corneal opacifi- 2. Gupta SK, De Becker I, Tremblay F, Guernsey DL, Neumann PE. cation associated with vascularization. Lens changes Genotype/phenotype correlations in aniridia. Am J Ophthalmol. 1998;126:203-210. were the most commonly associated anterior seg- 3. Neethirajan G, Solomon A, Krishnadas SR, Vijayalakshmi P, Sun- ment abnormality in this study, with cataract being daresan P. Genotype/phenotype association in Indian congenital aniridia. Indian J Pediatr. 2009;76:513-517. the most common (38.5%) lens finding, followed 4. Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson L. An- by subluxation, microspherophakia, lens coloboma, iridia: a review. Surv Ophthalmol. 1984;28:621-642. 5. Shaw MW, Falls HF, Neel JV. Congenital aniridia. Am J Hum and posterior lenticonus. The median age at which Genet. 1960;12:389-415. cataract was noted was 14 years, which shows that 6. Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M. WAGR syn- these eyes may have a predisposition for accelerated drome: a clinical review of 54 cases. Pediatrics. 2005;116:984- 988. cataractogenesis. A major factor limiting vision in 7. Edén U, Riise R, Tornqvist K. Corneal involvement in congenital patients with aniridia is foveal hypoplasia, which aniridia. Cornea. 2010;29:1096-1102.