Aniridia-associated Keratopathy Research Articles

Descemet Stripping Endothelial Keratoplasty for Congenital Aniridia: An Interesting and Challenging Story

Congenital aniridia is a rare condition affecting a wide range of ocular structures, from the ocular surface to the retina. We present the case of a 59-year-old woman with PAX6- and WT1-negative congenital aniridia who developed aniridia-associated keratopathy and progressive endothelial dysfunction with corneal decompensation after cataract surgery. The patient underwent successful ultrathin Descemet stripping endothelial keratoplasty. Despite the challenges faced with an unstable iridolenticular diaphragm, we were pleasantly surprised to see improvement not only of corneal edema and endothelial function but also of the whole cornea, including anterior corneal anatomy and appearance. In conclusion, endothelial transplantation in a patient with aniridia resulted in improvement of all the corneal structures from the endothelium to the stroma, epithelium, and possibly even the ocular surface.

Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?

Congenital PAX6-aniridia is a rare panocular disease resulting from limbal stem cell deficiency. In PAX6-aniridia, the downregulation of the retinol-metabolizing enzymes ADH7 (All-trans-retinol dehydrogenase 7) and ALDH1A1/A3 (Retinal dehydrogenase 1, Aldehyde dehydrogenase family 1 member A3) have been described in limbal epithelial cells (LECs) and conjunctival epithelial cells. The aim of this study was to identify the role of retinol derivates in the differentiation of human LEC and its potential impact on aniridia-associated keratopathy development. Human LEC were isolated from healthy donor corneas and were cultured with retinol, retinoic acid, or pan-retinoic acid receptor antagonist (AGN 193109) acting on RARα, β, γ (NR1B1, NR1B2 NR1B3) or were cultured with pan-retinoid X receptor antagonist (UVI 3003) acting on RXR α, β, γ (retinoid X receptor, NR2B1, NR2B2, BR2B3). Using qPCR, differentiation marker and retinoid-/fatty acid metabolism-related mRNA expression was analysed. DSG1 (Desmoglein 1), KRT3 (Keratin 3), and SPINK7 (Serine Peptidase Inhibitor Kazal Type 7) mRNA expression was downregulated when retinoid derivates were used. AGN 193109 treatment led to the upregulation of ADH7, KRT3, and DSG1 mRNA expression and to the downregulation of KRT12 (Keratin 12) and KRT19 (Keratin 19) mRNA expression. Retinol and all-trans retinoic acid affect some transcripts of corneal LEC in a similar way to what has been observed in the LEC of PAX6-aniridia patients with the altered expression of differentiation markers. An elevated concentration of retinol derivatives in LEC or an altered response to retinoids may contribute to this pattern. These initial findings help to explain ocular surface epithelia differentiation disorders in PAX6-aniridia and should be investigated in patient cells or in cell models in the future in more detail.

Long-Term Anatomical and Functional Survival of Boston Type 1 Keratoprosthesis in Congenital Aniridia.

Purpose: To analyze the long-term anatomical survival, functional survival, and complications of Boston type 1 keratoprosthesis (KPro) in the eyes with congenital aniridia-associated keratopathy (AAK).Methods: A retrospective review of 12 eyes with congenital aniridia that underwent a Boston type 1 KPro surgery was conducted. A Kaplan–Meier analysis was performed. Anatomical and functional success criteria were KPro retention and a best corrected visual acuity (BCVA) ≤1.3 LogMAR (≥0.05 decimal) at the end of a follow-up period. Postoperative complications were recorded.Results: The mean preoperative BCVA was 2.1 ± 0.9 (range: 3.8–1) LogMAR, and glaucoma was a comorbidity in all the cases. Five years after the surgery, the overall retention rate was 10/12 (83.3%), and 50% had functional success. Only three (25%) of the 12 cases did not achieve a BCVA ≤1.3 LogMAR. The cumulative probability of anatomical success was 92, 79, and 79% after 1, 5, and 10 years, respectively. The cumulative probability of functional success was 57 and 46% after 1 and 5 years, respectively. The mean anatomical and functional survival time was 10 ± 1.3 (95% IC = 7.5–12.3 years) and 3.8 ± 0.9 years (95% IC = 1.8–5.8 years), respectively. The most common postoperative complication was retroprosthetic membrane (RPM) formation in 8/16 cases (66%). The mean number of complications per case was 2.4 ± 1.8 (0–6).Conclusions: The Boston type 1 KPro is a viable option for patients with AAK with good anatomical and functional long-term results. Glaucoma is an important preoperative condition that affects functional results. Retroprosthetic membrane formation seems to have a higher incidence in this condition.

An attempt to optimize the outcome of penetrating keratoplasty in congenital aniridia-associated keratopathy (AAK)

PurposeTo propose an optimized microsurgical and medical approach to reduce the risk of complications after penetrating keratoplasty (PKP) in patients with aniridia-associated keratopathy (AAK).MethodsRetrospective observational case series of 25 PKP performed in 16 patients with AAK. Preoperative indications were endothelial decompensation and vascularized scars (68%) or graft failure (32%) due to limbal stem cell deficiency. The optimized approach included a combination of a small corneal graft size (around 7.0 mm), interrupted 10–0nylon sutures, simultaneous AMT as a patch, large bandage contact lens, temporary lateral tarsorrhaphy, postoperative autologous serum eye drops, and systemic immunosuppression. Main outcome measures included: visual acuity, transplant survival, and complications encountered during follow-up of 107 weeks on average.ResultsA complete modified keratoplasty scheme was used in 10 of 25 PKP (group 1), while at least one of the modifications was missing in the other 15 PKP (group 2). After 8 weeks of follow-up, the epithelium was closed in 23 eyes. Visual acuity improved in 19 eyes at 6 months of follow-up, and remained stable in six eyes. None of the eyes showed a decrease in visual acuity. At the last post-operative follow-up, this visual improvement persisted in 14 eyes and graft survival rate after 156 weeks (3 years) was 69% in group 1 versus 44% in group 2 (p = 0.39, log-rank test). Secondary corneal neovascularization (8%), scarring (4%), ulcer (4%), or graft rejection (8%) happened mostly in the second group which was missing at least one of the suggested modifications.ConclusionsPKP in congenital aniridia must be considered as a high-risk keratoplasty. An optimized therapeutic approach seems to be promising in order to reduce the postoperative complication rate in these most difficult eyes.

Dysfunction of the limbal epithelial stem cell niche in aniridia-associated keratopathy

PurposeAbnormalities in the limbal niche microenvironment have been suggested to be causally involved in aniridia-associated keratopathy (AAK), but histological analyses on the limbal structure and composition in AAK are lacking. Here, we investigated morphologic and molecular alterations of the limbal epithelial stem cell niche in human congenital aniridia. MethodsThe blind, buphthalmic and painful left eye of a 16-year old girl with congenital aniridia and juvenile glaucoma had to be enucleated because of uncontrolled intraocular pressure. The diagnosis of AAK was based on classical clinical features and partial limbal stem cell deficiency in the superior half. Genetic analysis identified a large heterozygous PAX6 gene deletion encompassing exons 11–15 as well as exon 9 of the neighboring ELP4 gene. Three limbal biopsies were taken from the superior, nasal and temporal regions to isolate and cultivate limbal epithelial progenitor cells and subject them to mRNA expression analyses. The globe was vertically bisected and processed for light and transmission electron microscopy and immunohistochemistry. ResultsComparative analysis of the superior and inferior limbal zones showed a gradual degradation of palisade structures associated with the transition from a hyperplastic to an attenuated corneal epithelium, inflammatory cell infiltrations and basement membrane irregularities. The clinically unaffected inferior part revealed no distinct stem cell clusters in the preserved palisade region, but a uniform population of hyperproliferative, undifferentiated progenitor cells in the basal/suprabasal layers of limbal and corneal epithelia, which gave rise to maldifferentiated epithelial cells exhibiting a conjunctival/epidermal phenotype and nuclear-to-cytoplasmic translocation of Pax6. The structure of the limbal niche was fundamentally perturbed, showing marked alterations in extracellular matrix composition, dislocation of atypical melanocytes lacking melanosomes and melanin, aberrant Wnt/β-catenin and retinoic acid signaling, and massive immune cell infiltration. ConclusionsConsidering the limitations of a single Case study, the findings suggest that ocular surface alterations in AAK are caused by a primary dysfunction and gradual breakdown of the limbal stem cell niche through Pax6-related effects on both melanogenesis and epithelial differentiation.

Outcomes of Human Leukocyte Antigen-Matched Allogeneic Cultivated Limbal Epithelial Transplantation in Aniridia-Associated Keratopathy-A Single-Center Retrospective Analysis.

Purpose:To assess the efficacy and safety of human leukocyte antigen–matched allogeneic cultivated limbal epithelial stem cell grafts in the treatment of aniridia-associated keratopathy (AAK).Methods:Six eyes of 6 patients with severe AAK received an allogeneic stem cell graft between January 2010 and March 2017. Anatomical and functional results were assessed at 6 months, 1 year, 2 years, and the final follow-up visit available. Safety analysis was performed by considering all perioperative and postoperative adverse events and additional surgeries required during the follow-up period.Results:The mean follow-up was 53.6 months (range 24–104 months). In most patients (80%), there was an early improvement of the keratopathy postoperatively, which slowly regressed during longer follow-up. At the final follow-up, 4 of the eyes were graded as failure and 1 eye was graded as partial success. Grading the sixth eye was not possible because of an adverse event. None of the patients maintained a total anatomical success in the long-term. Only 1 patient maintained a modest improvement in best-corrected visual acuity from hand motion to counting fingers. Four serious adverse events were recorded in 2 patients.Conclusions:Severe AAK remains a challenging condition to manage. Transplantation of allogenic ex vivo cultivated limbal stem cells may provide a temporary improvement in ocular surface stability, but anatomical and functional results are poor in the long-term. The eyes are prone to adverse events, and any surgical treatment should take this into consideration.

The tear film cytokine profile is altered in congenital Aniridia

AbstractIncreased levels of inflammatory cytokines in the tear fluid have been found in patients with dry eye disease (DED). Dry eye disease is highly prevalent in congenital aniridia and correlates with severity of aniridia associated keratopathy (AAK). As inflammation can damage the corneal epithelium, DED may initiate and worsen AAK. Additionally, inflammation also characterizes AAK and might exacerbate DED, creating a vicious circle. We carried out an extensive analysis of inflammatory cytokines in the tear fluid of aniridia patients and control subjects. The results were correlated with several clinical parameters, including tests for DED and meibomian gland dysfunction (MGD). The concentration of a number of pro‐inflammatory cytokines was significantly elevated in tear fluid from aniridia patients. Increasing level of these cytokines was related to parameters for MGD, including atrophy of meibomian glands, and shorter break‐up time of the tear film. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients and explain the high prevalence of MGD and DED in these patients.

Early phenotypic features of aniridia-associated keratopathy and association with PAX6 coding mutations

PurposeTo investigate corneal phenotype in aniridia-associated keratopathy (AAK) including its earliest manifestations, in relation to PAX6 mutational status. Methods46 subjects (92 eyes) with congenital aniridia from a German registry were examined using slit lamp biomicroscopy, anterior segment optical coherence tomography, contact esthesiometry and in vivo confocal microscopy. Cytogenetic analysis was conducted by Sanger sequencing of PAX6 exons and/or MLPA analysis. Measured parameters included AAK grade, distance-corrected visual acuity (DCVA), central corneal thickness (CCT), corneal sensitivity, subbasal nerve density, mature dendritic cell (DC) density and corneal epithelial phenotype. Results46 subjects (age range: 1–64 years) were examined, including 23 (50%) children under the age of 18. Five subjects (11.1%) with absent PAX6 coding mutation (non-PAX6 cases) had mild AAK (Grade 0–1) into the fourth decade of life and maintained corneal epithelial phenotype, greater subbasal nerve density (16.8 mm/mm2 vs. 3.58 mm/mm2, P = 0.01) and better corneal sensitivity (41 ± 11 mm vs. 28 ± 12 mm, P = 0.03) relative to those with PAX6 coding mutations. In five subjects, corneal endothelial cell density ranged from 3245 to 4399 cells/mm2. Independent of mutational status, an increased CCT, over tenfold increased mature DC density and reduced corneal sensitivity characterized all subjects. ConclusionsPAX6 coding mutations influence AAK phenotype and progression from the earliest stages of life. A minimal keratopathy present in 100% of congenital aniridia cases is independent of the specific mutation and consists of increased corneal thickness, reduced touch sensitivity, and increased ocular surface immune activity.

Management of Congenital Aniridia-Associated Keratopathy: Long-Term Outcomes from a Tertiary Referral Center

To report the outcomes of medical and surgical management for congenital aniridia-associated keratopathy (AAK) over a long-term follow-up period. Retrospective, comparative case series. Medical records of patients diagnosed with congenital aniridia were retrospectively reviewed. Age, sex, ethnicity, follow-up time, AAK stage, noncorneal abnormalities, ocular surgeries, and complications were recorded. The visual acuity equivalent (VAE), approximate Early Treatment Diabetic Retinopathy Study (appETDRS) letter score, was calculated using recorded Snellen visual acuities. A total of 92 eyes of 47 patients (31 females) with mean age of 48.0 ± 18.0 years and mean follow-up of 78.6 ± 42.2months were included. At the initial visit, 12 eyes (13%) were classified as Stage I AAK, 33 eyes (35.9%) were Stage II, 25 eyes (27.2%) were Stage III, 17 eyes (18.5%) were Stage IV, and 5 eyes (5.4%) were Stage V. Limbal stem cell transplantation (LSCT) and Boston keratoprosthesis (KPro) were frequently performed in eyes with Stages III-V. These advanced corneal surgeries significantly improved the median (95% confidence interval [CI]) of calculated appETDRS scores from 2 (0-20) to 26 (15-41) (Snellen values, 20/20,000 to 20/300; P = 0.0004). Patients with earlier Stages (I-II) of AAK were managed medically and had stable visual acuity through their final visits (appETDRS score of 26 [20-35] to 35 [26-35]; Snellen, 20/300 to 20/200; P > 0.05). The appETDRS VAE was significantly improved from 20 (0-35) to 30 (20-55), Snellen, 20/400 to 20/250, following LSCT (P= 0.021) and from 2 (0-20) to 2 (0-41) after KPro; Snellen, 20/20,000 VAE but with improved 95% CI after follow-up (P= 0.019). With proper characterization and staging of AAK, individualized medical and advanced surgical interventions preserves and improves visual acuity.

Meibomian gland dysfunction and keratopathy are associated with dry eye disease in aniridia

AimsTo investigate the aetiology and characteristics of dry eye disease (DED) in a Nordic cohort of patients with congenital aniridia.MethodsThirty-four Norwegian and one Danish subject with congenital aniridia and 21...

Stage-related central corneal epithelial transformation in congenital aniridia-associated keratopathy

PurposeTo relate central corneal epithelial phenotype to degree of keratopathy in a limbal stem cell deficient population. Methods37 patients (67 eyes) with aniridia-associated keratopathy (AAK) underwent corneal examination including slit lamp biomicroscopy to determine the Grade of AAK, Cochet-Bonnet esthesiometry, and in vivo confocal microscopy (IVCM) to assess morphology of the central corneal epithelium and subepithelial region. ResultsAAK Grade ranged from 1 (limbal involvement only) to 4 (total conjunctivalization), with progression from Grade 1 occurring after the age of 20. 30% of subjects had an asymmetric Grade between eyes. In early-stage AAK (Grades 1–2), central epithelial cells had mixed corneal-conjunctival phenotype, touch sensitivity and subbasal nerves diminished, and mature dendritic cells, inflammatory leukocytes, and blood vessels were present despite central transparency in the slit lamp. In later stages (Grades 3–4) of the LSCD, neural deficit and nerve function worsened, immune cell invasion increased, and lymphatic vessels were detected in several cases. Goblet cells and epithelial cysts were observed to varying degrees in all stages, but without clear association to AAK severity. The clinical grade and progression of AAK was strongly associated with the central corneal epithelial phenotype. ConclusionsAAK is associated with degradation of epithelial phenotype, a neural deficit, and immune compromised status even in the clear central cornea in the earliest stages. IVCM can aid in assessing whether the conditions for limbal stem cell maintenance are likely to exist, based on morphology of the central epithelial microenvironment.

Corneal Abnormalities in Congenital Aniridia: Congenital Central Corneal Opacity Versus Aniridia-associated Keratopathy

To clinically characterize and compare 2 types of corneal abnormalities in patients with congenital aniridia: (1) congenital central corneal opacity from birth (CCO) and (2) aniridia-associated keratopathy (AAK) that develops progressively with age. Retrospective cohort study. Medical records of Korean patients who were diagnosed with congenital aniridia at Seoul National University Hospital between 1991 and 2016 were reviewed. Prevalence of corneal abnormalities (CCO and AAK), other ocular and systemic comorbidities, severity of AAK depending on the age, logarithm of the minimum angle of resolution (logMAR) visual acuities, and types and results of surgical intervention were collected. Among a total of 275 eyes (138 patients), 13% (35 eyes, 20 patients) had CCO and 25% (68 eyes, 35 patients) developed AAK. The AAK became prominent at a mean of 21.6 years of age, and the severity progressed with age. Glaucoma was more prevalent in aniridia patients with CCO (74%), compared to those with AAK (37%) (P= .0003). Cataract frequently occurred in patients with AAK (78%), who required cataract surgeries at mean 26.6 years. The logMAR visual acuity was worse in patients with CCO (2.04 ± 0.71) than in those with AAK (1.29 ± 0.62) (P < .0001). Penetrating keratoplasty was performed in 6 eyes with CCO, and the graft survival was 33.3% during mean 45months of follow-up (range 14-79months). In total, 13% of aniridia patients had CCO at birth, while 25% progressively developed clinically significant AAK with age. The visual outcome was worse in patients with CCO than in those with AAK.

Clinical and morphological manifestations of aniridia-associated keratopathy on anterior segment optical coherence tomography and in vivo confocal microscopy

PurposeThe study aimed to evaluate clinical and morphological changes in the limbal palisades of Vogt (POV) at different stages of aniridia-associated keratopathy (AAK) and to assess possible utility of anterior segment optical coherence tomography (AS-OCT) for the visualization of limbal progenitor structures as it correlates to laser scanning confocal microscopy (LSCM) data. MethodsThe study involved 32 patients (59 eyes) with congenital aniridia. AAK stage was defined based on biomicroscopy. Assessment of limbal zone and detection of POVs in identical areas was performed by LSCM (HRT3) and AS-OCT (RTVue XR Avanti) using 3D Cornea (En Face mode) and Cornea Cross Line protocols. ResultsIntact and changed POVs were found in 8/8 stage 0 eyes, in 1/21 stage I and 2/13 stage II eyes. Spearman's correlation coefficient in assessing the consistency of the POV diagnostic results by LSCM and AS-OCT for the inferior limbus was rS = 0.85 (P < 0.05), for the superior limbus – rS = 0.53 (P < 0.05). AS-OCT was less sensitive for detection of partially present POVs in superior limbus. The negative correlation between AAK stage and POV preservation was determined (rS = −0.5, P < 0.05). There was no correlation between AAK stage and patient age (rS = 0.235, P = 0.209). Three patients with PAX6 3′ deletion showed stage 0 AAK with intact or slightly disturbed POVs morphology and transparent cornea. ConclusionAS-OCT may be an additional diagnostic tool for POV visualization in vivo in aniridic patients. Its diagnostic accuracy is subject to selection of anatomic region, nystagmus and the degree of POV degradation.

Diagnostic capabilities of optical coherence tomography and confocal laser scanning microscopy in studying manifestations of aniridia-associated keratopathy

to investigate the possible use of anterior segment optical coherence tomography (AS-OCT) and laser scanning confocal microscopy (LSCM) for visualization of limbal progenitor structures and epithelial changes at different stages of aniridia-associated keratopathy (AAK) and to analyze genotype-phenotype correlations of corneal damage. Thirty-four patients (63 eyes) with congenital aniridia (CA) were subjected to epithelial cell density measurement in the central cornea as well as epithelial surface assessment with limbal palisades of Vogt (POV) detection in the corresponding sites of the two corneas. For that, LSCM (HRT3) and AS-OCT (RTVue XR Avanti) were performed. Central corneal and epithelial thicknesses were measured using the Pachymetry protocol. There has been found an increase in the central corneal thickness (CCT) of CA patients, which correlated with the stage of AAK, and a decrease in the central epithelial thickness as compared with healthy subjects (p<0.05). The difference between the basal and wing epithelial cells density in eyes with stages I and II AAK and normal cells density at stage 0 AAK was statistically significant (p<0.05). Intact or disturbed POV were detected in all patients with PAX6 3' deletion. At that, AS-OCT findings highly agreed with LSCM images for both the inferii (rS=0.85, p<0.05) and superior limbi (rS=0.53, p<0.05). A negative correlation was established between the stage of AAK and in vivo morphology of POV (rS=-0.5, p<0.05). However, no correlation was found between the stage of AAK and patient's age (rS=0.169, p=0.174). AS-OCT and LSCM are both important diagnostic tools for corneal surface monitoring in patients with limbal stem cells deficiency.

The clinical characterization and surgical correction of blepharoptosis associated with congenital aniridia.

To document the clinical characteristics and describe our management of patients with blepharoptosis associated with congenital aniridia. Consecutive retrospective case series of patients with congenital aniridia seen at a single institution (Cincinnati Eye Institute) from 1963 to 2010. Surgical correction was performed by 2 surgeons (J.A.N. and R.C.K.). Ptosis associated with congenital aniridia is marked with decreased levator function. Significant comorbid ophthalmologic disease was invariably present, particularly aniridia-associated keratopathy. Complications, most often keratopathy, were common, even following conservative correction. The degree of ptosis is significant, and levator function is typically reduced. Ocular surface viability appears to play a key role in preoperative, intraoperative, and postoperative management. While we are aware that congenital aniridia is rather rare, we believe these recommendations are generalizable to patients with severe ocular surface disease.

Treatment of Congenital Aniridia Associated with Subluxated Infantile Cataract

A 5 year old boy was presented at Eye clinic University clinical center Tuzla with congenital aniridia in both eyes. Clinical examination revealed visual acuity of 0,08 without correction in right and 0.7 with -5.0 Dsph and -1.0 Dcyl Axx 109° in left eye. Opthalmologic examination showed bilateral aniridia associated with moderate cataract in the right and incipient cataract in the left eye. In the right eye, zonular weakness with incipient capsular displacement and esotropia of Δ6º, were noted. The patient underwent phacoemulsification, implantation of capsular tension ring and Artificial Iris implant in the capsular bag. Phacoemulsification went uneventful and early postoperative recovery was successful with no signs of aniridia-associated keratopathy development and normal values of intra ocular pressure. Patient was not motivated for operation of the left eye and it was corrected with soft contact lens. Six month after the operation visual acuity in the right eye improved to 0.9 with +1.25Dsph and maintained stable in left eye, with complete elimination of esotropia and signs of binocular vision restoration. Small incision cataract extraction with IOL and Artificial Iris implantation in one procedure can be used to correct congenital aniridia and cataract with significant visual function improvement.

A Review of the Clinical and Genetic Aspects of Aniridia

Aniridia classically presents with a bilateral congenital absence or malformation of the irides, foveal hypoplasia, and nystagmus, and patients tend to develop visually significant pre-senile cataracts and keratopathy. Additionally, they are at high risk for developing glaucoma. Classic aniridia can be genetically defined as the presence of a PAX6 gene deletion or loss-of-function mutation that results in haploinsufficiency. Variants of aniridia, which include a condition previously referred to as autosomal dominant keratitis, are likely due to PAX6 mutations that lead to partial loss of PAX6 function. Aniridia-associated keratopathy (AAK) is a progressive and potentially debilitating problem affecting aniridic patients. The current treatments for AAK are to replace the limbal stem cells through keratolimbal allograft (KLAL) with or without subsequent keratoplasty for visual rehabilitation, or to implant a Boston type 1 keratoprosthesis. Future therapies for AAK may be aimed at the genetic modification of corneal limbal stem cells.

Cataract development in Norwegian patients with congenital aniridia

Editor, Congenital aniridia is caused by mutation of the PAX 6 gene, the so-called master gene in ocular development. Although cataract has been reported in several aniridia cohorts (Nelson et al. 1984; Sale et al. 2002; Hingorani & Moore 20082009; Abouzeid et al. 2009; Park et al. 2010; He et al. 2012), the timing and detailed phenotype of cataract in aniridia have not been well described. Here, we report the onset of cataract, timing of cataract surgery and phenotypic features of cataract in a Norwegian aniridia cohort. A cohort of 26 Norwegian patients (52 eyes) with ngenital aniridia was examined on a single occasion, after obtaining written informed consent and ethical approval from the Regional Committee for Medical and Health Research Ethics, Oslo. Medical records were examined to detail cataract presence and surgical intervention. Digital slit lamp photographs of the lens and visual assessment were used to analyse the type and development of cataract, and aniridia-associated keratopathy (AAK) was characterized according to our previously published grading scale (Eden et al. 2012). Mean patient age was 29 years (range: 4–63 years). Only three eyes were phakic with clear lenses; the remaining eyes had either cataract or had been operated on for cataract. The youngest individual with cataract was 4 years old at examination, but congenital or early onset cataract was documented in medical records of five patients (six eyes). Of 12 patients with nonoperated cataract, five (nine eyes) had lens luxation upwards. Of 14 patients, 27 eyes had glaucoma. Those least affected presented with a discrete posterior polar cataract. In other cases, a discrete subcapsular opacification of varying density or opacification extending radially from the mid-periphery of the posterior capsule was found in addition to the polar cataract. A posterior subcapsular mid-peripheral ring of opacification was observed, in some also combined with a more substantial polar cataract. The size and density of the opaque ring varied (Fig. 1). Findings in other patients included nuclear cataract (both turbid and yellow-brownish), one generalized subcapsular oedema (mature cataract) and one with a dehydrated opaque lens (hypermature cataract) (Fig. 1). In two patients, an anterior polar cataract was identified one of which had an additional posterior subcapsular opacification (Fig. 1). Fig 1 Developmental patterns of cataract in aniridia patients. (A) Early stage discrete posterior subcapsular cataract. (B–E) The posterior subcapsular cataract is denser. A posterior subcapsular opacification develops on the capsule in the ... Of the 52 eyes examined, 25 had had surgical intervention (cataract, glaucoma or both). Nine patients (13 eyes) had cataract surgery only, six patients (eight eyes) both cataract and glaucoma surgery and three patients (four eyes) glaucoma surgery only. At the time of cataract surgery, 7 of 12 operated patients were under the age of 19 years and 4 of these were under the age of 10. Secondary cataract was observed in four patients (six eyes).Of the 25 eyes with surgical intervention, eight eyes (30%) had AAK affecting visual acuity compared to 8/25 eyes (32%) in the group of eyes without intraocular surgery. No clear trend could be found towards an increased prevalence of AAK in operated eyes. Cataract is common in aniridia, with over 90% prevalence in our cohort, similar to a Korean cohort with 60 eyes where 88% had cataract or were operated for cataract (Park et al. 2010). Cataract prevalence in aniridia in the literature varies from 50 to 85% (Nelson et al. 1984). Patients in our cohort not operated for cataract showed a distribution of lens opacities that could be interpreted as a pattern of cataract development. A discrete posterior polar opacity seems to emerge first. The posterior location of polar opacities has been reported previously (Yamn et al. 2011; Jin et al. 2012). The next phase is an additional subcapsular opacification in the mid-periphery. These opacities then increase in density and size, radiate to the polar region and are always limited to the posterior subcapsular region. They eventually form a ring on the posterior capsule.

In vivo confocal microscopy of congenital aniridia-associated keratopathy

To explore the in vivo morphological changes of cornea and limbus in aniridia-associated keratopathy (AAK). Three cases of AAK were examined with the application of in vivo confocal microscopy (IVCM). Abnormal structure of wing and basal layer of epithelium, the loss of subbasal nerves, and the presence of goblet cells at central cornea could be identified in the most severe case, along with the absence of Vogt palisades. The less extent of abnormalities in corneal epithelial cells, subbasal nerve, and Vogt palisades were visible in the moderate or mild cases. The morphological changes of cornea and limbus vary in AAK, and IVCM is a promising tool to determine the degree of limbal stem cell deficiency in patients with AAK.

Complications and Visual Prognosis in Children with Aniridia

To characterize the ophthalmological findings, assess surgical outcomes, and review visual outcomes in aniridia. A retrospective case review was performed and data were collected, including patient demographics, incidence of aniridia-associated keratopathy, glaucoma, cataract, retinal breaks or detachments, optic nerve hypoplasia, macular hypoplasia, poor vision, and nystagmus. All outcomes from surgery, including penetrating keratoplasty, trabeculectomy, Ahmed valve insertion, and cataract extraction, were recorded. Six children (12 eyes) had corneal abnormalities, 4 had optic nerve hypoplasia, 9 had nystagmus, and 2 had retinal detachments. Four patients (7 eyes) required penetrating keratoplasty. Five patients (9 eyes) developed glaucoma and only 1 of the 4 trabeculectomies performed succeeded. Of the 6 Ahmed valve procedures performed, all succeeded in maintaining a satisfactory intraocular pressure but some required needling and 5-fluorouracil. Eight patients developed cataract and 7 required surgery. Visual outcomes were poor despite treatment. Nine patients had Snellen acuity of 6/60 or less and required low visual aids to function. Aniridia is a disorder that requires multiple surgeries. It has a poor visual prognosis despite early diagnosis and aggressive management. Newer techniques such as Ahmed valves and Boston keratoprostheses offer hope, but its proliferative nature makes treatment difficult.