The purpose is to highlight the surgical modifications that are undertaken for a safe cataract surgery when associated with anterior segment dysmorphology. Surgical modifications that are undertaken in a case of congenital cataract complicated with congenital anterior segment dysmorphology such as microcornea, congenital corneal opacity, aniridia, anterior and posterior lenticonus of the lens, and persistent fetal vasculature are described. Careful preoperative assessment is crucial to anticipate and plan for intraoperative and postoperative challenges that may arise during cataract surgery in the presence of anterior segment dysmorphology. Surgical adjustments in cataract surgery when associated with anterior segment dysmorphology should be tailored to each individual case and the surgeon's expertise.

PITX3 has been reported to be associated with congenital cataracts, anterior segment mesenchymal dysgenesis, Peters' anomaly, and microphthalmia. In this case, an infant with unilateral buphthalmos, corneal staphyloma and corneal fistula carrying a variant in PITX3 was reported. We describe a 4-month-old female infant who was referred to our Eye Clinic because of gradual enlargement of the eyeball in the right eye and whitish opacity in both eyes. Buphthalmos with long axial length (22.04 mm), macrocornea with diffuse corneal oedema and opacity (14.50 mm*14.50 mm) and high intraocular pressure (23.78 mmHg) were detected in the right eye. Microphthalmia with short axial length (16.23 mm), microcornea with diffuse corneal oedema and opacity (7.50 mm*6.50 mm) were detected in the left eye. A 360° trabeculotomy was performed for the right eye. However, corneal staphyloma and corneal fistula in the right eye were detected 6 months after the surgery. A variant in exon 4 of PITX3 (c.640_656dup (p. Gly220Profs*95)) was identified in the proband but was not detected in her healthy parents. A novel phenotype characterized by unilateral buphthalmos, corneal staphyloma and corneal fistula in an infant were reported to be associated with PITX3 in our study. Our study expands the scope of the clinical heterogeneity of PITX3 variants. It also improves our understanding and increases the attention given to patients with PITX3 variants.

International initiatives to prevent childhood blindness have highlighted the importance of early, effective intervention for congenital and infantile cataract. In the UK, intraocular lens implantation has been widely adopted by surgeons to treat these conditions. However, evidence about the benefits and risks of this technique in different age groups is limited. The IoLunder2 study assessed outcomes following primary intraocular lens implantation in children aged 2 years and younger with congenital or infantile cataract. The IoLunder2 study was a prospective observational cohort study done at 31 sites in the UK and Ireland. Eligible children were aged 2 years or younger who had cataract surgery concurrently with intraocular lens implantation or conventional treatment (aphakic correction with contact lenses or glasses) after cataract surgery between Jan 1, 2009, and Dec 31, 2010. Children with significant ocular comorbidity precluding lens implantation, defined by the presence of complex persistent fetal vasculature, other ocular structural anomalies, severe microcornea (horizontal corneal diameter <9·5 mm), or severe microphthalmos (axial length <16 mm), were excluded from the analysis of the key outcomes. Postoperative visual rehabilitation was assessed at 1, 3, and 5 years after surgery with a 4m logarithm of the minimum angle of resolution (logMAR) notation test. Best corrected visual outcome (acuity) overall was assessed 5 years after surgery for children with bilateral and unilateral cataract. We also used multivariable logistic and linear regression to model the association between intraocular lens implantation and outcomes of interest (vision, glaucoma, and visual axis opacity). A total of 256 eligible children were recruited; two had incomplete data and were excluded. 158 of the 254 included children (102 [65%] with bilateral cataract and 56 [35%] with unilateral cataract) had no significant ocular morbidity and were analysed for the key outcomes. Primary intraocular lens implantation was done in 88 (56%) of 158 children (50 children with bilateral cataract and 38 children with unilateral cataract). 70 (44%) of 158 children had conventional treatment (52 with bilateral cataract and 18 with unilateral cataract). Overall median visual acuity at 5 years was 0·34 logMAR (IQR 0·20-0·54) for children with bilateral cataract and 0·70 logMAR (IQR 0·3-1·3) in the operated eye for children with unilateral cataract. Primary intraocular lens implantation was not associated with better visual outcome than conventional treatment in children with bilateral cataract (adjusted coefficient -0·1, 95% CI -0·5 to 0·3, p=0·48) or unilateral cataract (adjusted coefficient -0·3, -0·6 to 0·2, p=0·36), or reduced incidence of postoperative glaucoma in children with bilateral cataract (adjusted odds ratio [OR] 0·5, 0·10 to 1·80, p=0·28), but was associated with a five times higher risk of reoperation for visual axis opacity requiring general anaesthesia in children with bilateral cataract (adjusted OR 5·94, 95% CI 2·14-16·47, p=0·001) and a 20 times higher risk in children with unilateral cataract (20·15, 3·01-134·00, p=0·001). The findings of this cohort study indicate that intraocular lens implantation does not confer better vision or protection against postoperative glaucoma, and conversely increases the risk of requiring early reoperation in children younger than 2 years with bilateral or unilateral cataract. The routine use of intraocular lens implantation in this age group cannot be recommended. National Institute for Health Research, Ulverscroft Foundation, and the Academy of Medical Sciences.

Mutations in the transcription factor genes FOXE3, HSF4, MAF, and PITX3 cause congenital lens defects including cataracts that may be accompanied by defects in other components of the eye or in nonocular tissues. We comprehensively describe here all the variants in FOXE3, HSF4, MAF, and PITX3 genes linked to human developmental defects. A total of 52 variants for FOXE3, 18 variants for HSF4, 20 variants for MAF, and 19 variants for PITX3 identified so far in isolated cases or within families are documented. This effort reveals FOXE3, HSF4, MAF, and PITX3 to have 33, 16, 18, and 7 unique causal mutations, respectively. Loss-of-function mutant animals for these genes have served to model the pathobiology of the associated human defects, and we discuss the currently known molecular function of these genes, particularly with emphasis on their role in ocular development. Finally, we make the detailed FOXE3, HSF4, MAF, and PITX3 variant information available in the Leiden Online Variation Database (LOVD) platform at https://www.LOVD.nl/FOXE3, https://www.LOVD.nl/HSF4, https://www.LOVD.nl/MAF, and https://www.LOVD.nl/PITX3. Thus, this article informs on key variants in transcription factor genes linked to cataract, aphakia, corneal opacity, glaucoma, microcornea, microphthalmia, anterior segment mesenchymal dysgenesis, and Ayme-Gripp syndrome, and facilitates their access through Web-based databases.

PurposeTo reveal the underlying genetic defect in two four-generation Chinese families with aniridia and explore the pathologic mechanism.MethodsFull ophthalmic examinations were performed in two families with aniridia. The PAX6 gene was directly sequenced in patients of two families, and the detected variants were screened in unaffected family members and two hundred unrelated healthy controls. Real-time quantitative PCR was used to explore pathologic mechanisms of the two variants.ResultsAniridia, cataract, and oscillatory nystagmus were observed in patients of the two families. In addition, we observed corneal opacity and microphthalmus in family 1, and strabismus, left ectopia lentis, microphthalmus, and microcornea in family 2. Sanger sequencing detected a novel 1-bp duplication (c.50dupA) in family 1 and a novel 2-bp splice site deletion (c.765+1_765+2delGT) in family 2. Sequencing of cDNA indicated skipping of exon 9 caused by the splice site deletion, being predicted to cause a premature stop codon, as well as the duplication. The PAX6 mRNA significantly lower in patients with aniridia than in unaffected family members in both families, suggesting that the duplication and splice site deletion caused nonsense-mediated mRNA decay.ConclusionsOur study identified two novel PAX6 variants in two families with aniridia and revealed the pathogenicity of the variants; this would expand the variant spectrum of PAX6 and help us better understand the molecular basis of aniridia, thus facilitating genetic counseling.