Eur J Ophthalmol22 (2012; :1) 104-110 DOI: 10.5301/EJO.2011.8318 ORIGINAL ARTICLE Glaucoma and frequency of ocular and general diseases in 30 patients with aniridia: a clinical study Eugen Gramer1*, Constantin Reiter1*, Gwendolyn Gramer2 1Department of Ophthalmology, University Würzburg, Würzburg - Germany 2University Hospital for Pediatric and Adolescent Medicine, University Heidelberg, Heidelberg - Germany Department of Ophthalmology, University Würzburg, Würzburg - Germany PURPOSE. To evaluate the following in patients with aniridia: age at first examination at the University Eye Hospital and age at diagnosis of glaucoma; visual acuity; frequency of family history of aniridia; and frequency of ocular and general diseases associated with aniridia. METHODS. This was a consecutive examination of 30 unrelated patients with aniridia and retrospective evaluation of ophthalmologic, pediatric, and internal findings. The relative frequency of age at glauco- ma diagnosis within decades was evaluated for the 20 patients with aniridia and glaucoma. Statistical analysis was performed using the Mann-Whitney test. RESULTS. Relative frequency of the age of patients with aniridia at time of glaucoma diagnosis within the following decades was as follows: from birth to 9 years: 15%, 10-19: 15%, 20-29: 15%, 30-39: 15%, 40-49: 35%, and 50-59: 5%. Visual acuity in the better eye of 20/100 or less was found in 60%. Family history of aniridia was found in 33.3% of patients, with 1-4 relatives with aniridia. A total of 76.7% of patients had congenital cataract, and 66.7% had glaucoma. Mean maximum intraocular pressure of the 20 patients with glaucoma was 35.9 mmHg in the right and 32.6 mmHg in the left eye. A total of 53.3% had nystagmus, 26.6% corneal opacifications, 16.7% bilateral lens dislocation upwards, 6.7% optic nerve hypoplasia, 3.3% poor foveal development, and 3.3% Wilms tumor. CONCLUSIONS. Up to the age of 40 years, 15% of patients were diagnosed with glaucoma per age de- cade. Frequent bilateral glaucoma and similar bilateral height of intraocular pressure suggest a genetic glaucoma disposition with malformation at Schlemm canal, besides possible sequential anatomic changes in the chamber angle. Associated ocular abnormalities limit visual prognosis. KEY WORDS. Aniridia, Congenital cataract, Glaucoma, PAX6, Wilms tumor Accepted: April 3, 2011 INTRODUCTION fied mutation of PAX6 gene (1), which provides evidence for genetic heterogeneity in aniridia. Aniridia is very rare, with an Aniridia is a panocular human eye malformation caused by incidence between 1:64,000 and 1:100,000 births and may heterozygous mutations within the Paired Box gene 6 (PAX6) be found in isolation or in combination with other syndromes or cytogenetic deletions of chromosome 11p13 that encom- (2). In two-thirds of patients, aniridia is inherited in an auto- pass PAX6. PAX6 has a wide expression in the developing somal dominant way with complete penetrance, but varying eye, in the neuroectoderm and the surface ectoderm, and expressivity. One-third of cases are sporadic (2). Fluorescent therefore in their derivates, e.g., lens, cornea, and retina. Al- in situ hybridization (FISH) is the chosen method to analyze though 80% of patients with aniridia demonstrate a PAX6 mutations in sporadic cases of aniridia (3), which lets the gene mutation, there are few reported cases with no identi- examiner assess the exact extent of the deletions and the risk of the development of Wilms tumor. *These authors contributed equally to this work. The aim of this study was to evaluate the following in 30 104 © 2011 Wichtig Editore - ISSN 1120-6721 Gramer et al patients with aniridia: 1) age of the patient at first examina- Visual acuity tion of aniridia at the University Eye Hospital Würzburg; 2) age at diagnosis of glaucoma (in 20 patients with aniridia Evaluation of visual acuity was based on the patients’ last and glaucoma), providing indirect information on the onset examination with best-corrected distance vision (digit- of glaucoma in aniridic patients; 3) visual acuity at last ex- based visual acuity chart). Visual field examinations were amination; 4) frequency of family history of aniridia; and 5) not possible in all patients due to infancy, corneal opaci- frequency of ocular and general diseases associated with ties, or reduced visual acuity. Therefore, visual field results aniridia: congenital cataract, glaucoma, nystagmus, cor- were not included in the evaluation. neal opacification, lens dislocation, optic nerve hypoplasia, IOP was measured with Goldmann applanation tonom- poor foveal development, and frequency of Wilms tumor. etry, and gonioscopy was performed with the Goldmann gonioscope. Optic disc evaluation was performed by indi- rect ophthalmoscopy and, if feasible, with the 78-D lens. In MATERIALS AND METHODS patients who underwent examinations in the past decade, in addition quantitative disc analysis was performed using Consecutive ophthalmologic examination of 30 patients different computerized optic nerve head analyzers, e.g., with aniridia was performed during the last 29 years with Heidelberg Retina Tomograph (HRT). Photodocumentation standardized documentation. Age of the patient at first ex- was performed in most of the patients. Mann-Whitney test amination at the University Eye Hospital Würzburg and age was used for statistical analysis. of the patients with glaucoma at diagnosis of glaucoma, maximum intraocular pressure (IOP), and family history of aniridia were requested from patients and their ophthal- RESULTS mologists. This study presents a retrospective evaluation of the files of these patients and a prospective inquiry of Age of the patients at first examination at the the age at glaucoma diagnosis and evaluates ophthalmo- University Eye Hospital logic, pediatric, and internal findings. The relative frequency of age at diagnosis of glaucoma within age decades was calculated for the 20 patients with aniridia and glaucoma. Mean age at first examination in our hospital in 30 patients Some patients had first diagnosis of glaucoma at hospital with bilateral aniridia was 28±19.3 years. Age distribution visit. If no information on age at diagnosis of glaucoma was at first examination in our hospital was as follows: up to 9 available, the age at diagnosis of glaucoma at examination years 23.3%, 10-19 years 13.3%, 20-29 years 13.3%, 30- in the clinic was used. 39 years 10%, 40-49 years 26.7%, 50-59 years 3.3%, 60- 69 years 6.7% (Fig. 1). A total of 37% of all patients were Definition of aniridia in family history first referred to our hospital before the age of 20 years. Family history was defined as the patient or his or her rel- Age of patients with glaucoma at glaucoma di- atives reporting aniridia in one or more first- or second- agnosis degree relatives as diagnosed by an ophthalmologist. The number of relatives with aniridia was requested. Many pa- Age distribution of the 20 aniridic patients with glaucoma tients were seen only one time because ophthalmologists at diagnosis was as follows: up to 9 years 15%, 10-19 recommended a second opinion. Family history was reas- years 15%, 20-29 years 15%, 30-39 years 15%, 40-49 sessed for patients with follow-up. Several patients were years 35%, 50-59 years 5% (Fig. 2). There is a high vari- seen before molecular-genetic diagnostics was available. ability in the onset of glaucoma in patients with aniridia. All patients were advised at the first visit to inform their rel- In 30% of patients glaucoma was diagnosed before the atives about the necessity of ophthalmologic screening for age of 20 years, showing that every third aniridic patient aniridia. A total of 29 patients were included in the statisti- with glaucoma had glaucoma onset before the age of 20 cal analysis because for one patient without glaucoma only years. There was no significant difference in the mean age data on family history and visual acuity were available. at first examination at our hospital between patients with © 2011 Wichtig Editore - ISSN 1120-6721 105 Associated diseases in 30 patients with aniridia Fig. 1 - Frequency distribution of age at first examination at the Uni- Fig. 2 - Age of the patient at glaucoma diagnosis in 20 patients with versity Eye Hospital within age decades in 29 patients with aniridia. aniridia and glaucoma. Frequency of diseases associated with aniridia Associated diseases were congenital cataract in 76.7% and glaucoma in 66.7%; out of these, 10% had unilateral and 90% bilateral glaucoma. Only one of these patients had congenital glaucoma. Mean maximum IOP of the 20 glaucoma patients was 35.9 mmHg in the right and 32.6 mmHg in the left eye. A total of 53.3% had nystagmus, 26.6% corneal opacifications, 16.7% bilateral lens dislo- cation upwards, 6.7% optic nerve hypoplasia, 3.3% poor foveal development, and 3.3% Wilms tumor (Fig. 3). DISCUSSION Fig. 3 - Relative frequency of ocular and systemic diseases associ- ated with aniridia. Glaucoma in aniridia and age of patients at glau- coma diagnosis glaucoma and patients without glaucoma (29.6±16.6 years vs 24.7±25.1 years) (p=0.49). The main aim of our study was to evaluate the age at onset of glaucoma and to calculate the frequency of age at diag- Visual acuity nosis within age decades in 20 aniridic patients with glau- coma, examined consecutively. With the same approach, Decreased vision in the better eye of 20/100 or less was we evaluated the age at diagnosis in different types of found in 60% of all patients. glaucoma in more than 2,000 patients with glaucoma (4). This allows a comparison between the age at diagnosis Family history within decades between aniridic patients with glaucoma and patients with, e.g., primary open-angle glaucoma or Family history of aniridia was found in 10 of 30 unrelated pigmentary glaucoma.