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A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. 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 dry eye disease in these patients.
Purpose
To investigate the association between
PAX6
genotype and macular morphology in congenital aniridia.
Methods
The study included 37 participants (15 males) with congenital aniridia (aged 10–72 years) and 58 age-matched normal controls (18 males). DNA was isolated from saliva samples.
PAX6
exons, intron/exon junctions, and known regulatory regions were amplified in PCR and sequenced. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect larger deletions or duplications in
PAX6
or known
cis
-regulatory regions. Spectral-domain optical coherence tomography images were acquired and segmented semiautomatically. Mean thicknesses were calculated for inner and outer retinal layers within the macula along nasal and temporal meridians.
Results
Mutations in
PAX6
or regulatory regions were found in 97% of the participants with aniridia. Foveal hypoplasia was observed in all who had a mutation within the
PAX6
gene. Aniridic eyes had thinner outer retinal layers than controls, but with large between-individual variation (mean ± SD, 156.3 ± 32.3 µm vs 210.8 ± 12.3 µm,
P
< 0.001). Parafoveal and perifoveal inner and outer retinal layers were thinner in aniridia. Participants with mutations in noncoding
PAX6
regions had thicker foveal outer retinal layers than those with mutations in the
PAX6
coding regions (
P
= 0.04) and showed signs of postnatal development and maturation. Mutations outside the
PAX6
gene were associated with the mildest retinal phenotypes.
Conclusions
PAX6
mutations are associated with significant thinning of macular inner and outer retinal layers, consistent with misdirected retinal development resulting in abnormal foveal formation and reduced number of neurons in the macula, with mutations in
PAX6
coding regions giving the worst outcome.
This study indicates a diminution of Crohn's disease activity with time, as demonstrated by no need for intestinal repeat resection more than 25 years after the first resection.
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