Recurrent ectasia in corneal grafts and outcomes of repeat keratoplasty for keratoconus.

AIM: To analyse cases of recurrent ectasia in donor corneas after penetrating keratoplasty (PK) for keratoconus. METHODS: Data on 25 patients (36 eyes) with recurrent ectasia were retrospectively analysed in this study. The main outcome measures were time to development of recurrent ectasia after first PK for keratoconus, change in keratometric sphere and astigmatism between final suture removal and development of recurrent ectasia, status of regrafts for recurrent ectasia, and histopathology of grafts excised for recurrent ectasia. RESULTS: The age at first PK was 32.6 (SD 8.5) years, and ectasia developed 21.9 (7.0) years after PK. The mean keratometric sphere and cylinder increased by 4.2 D and 3.0 D, respectively, between final suture removal and diagnosis of recurrent ectasia. Ectasia was often preceded by thinning without bulging of the recipient stroma at the graft-host junction. Fifteen eyes (13 patients) were regrafted for recurrent ectasia, and histopathology of the excised grafts showed changes characteristic of keratoconus in the donor tissue in all cases. Two regrafts (two eyes of one patient) developed ectasia again, with one eye requiring a third PK to improve vision. CONCLUSIONS: Recurrent ectasia was diagnosed on average two decades after PK. Ectatic changes were often bilateral and occasionally recurred after regrafting, suggesting that host cellular and/or biochemical factors may be responsible. Repeat PK for recurrent ectasia is successful in the intermediate term.

Diamond burr superficial keratectomy for recurrent corneal erosions.

AIMS: To evaluate the efficacy and safety of diamond burr superficial keratectomy in the treatment of recurrent corneal erosions. METHODS: A retrospective review of 54 eyes (47 patients) with recurrent corneal erosions treated with diamond burr superficial keratectomy. Preoperative and postoperative visual acuities and refractions, slit lamp examination findings, and the incidence of recurrent erosion after keratectomy were studied. Specular microscopy was also performed in six patients before and after surgery. RESULTS: 30 eyes had underlying map dot fingerprint anterior basement membrane corneal dystrophy, while 24 eyes did not. Postoperative follow up time ranged from 3 to 53 months (mean 12.3 months). Corneal erosion recurred in three eyes (6%) after diamond burr superficial keratectomy. This procedure improved the best corrected visual acuity from 20/26 to 20/22 by logMAR statistical evaluation (p=0.002) and caused very little change in the refractive spherical equivalent. No endothelial cell loss or changes in morphology were noted on specular microscopy. CONCLUSION: Diamond burr superficial keratectomy appears to be an effective and safe method of treating recurrent erosions and is a good alternative therapy to needle stromal micropuncture, Nd:YAG induced epithelial adhesion, and excimer laser surface ablation.

Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration.

The NRL gene encodes an evolutionarily conserved basic motif-leucine zipper transcription factor that is implicated in regulating the expression of the photoreceptor-specific gene rhodopsin. NRL is expressed in postmitotic neuronal cells and in lens during embryonic development, but exhibits a retina-specific pattern of expression in the adult. To understand regulation of NRL expression and to investigate its possible involvement in retinopathies, we have determined the complete sequence of the human NRL gene, identified a polymorphic (CA)n repeat (identical to D14S64) within the NRL-containing cosmid, and refined its location by linkage analysis. Since a locus for autosomal recessive retinitis pigmentosa (arRP) has been linked to markers at 14q11 and since mutations in rhodopsin can lead to RP, we sequenced genomic PCR products of the NRL gene and of the rhodopsin-Nrl response element from a panel of patients representing independent families with inherited retinal degeneration. The analysis did not reveal any causative mutations in this group of patients. These investigations provide the basis for delineating the DNA sequence elements that regulate NRL expression in distinct neuronal cell types and should assist in the analysis of NRL as a candidate gene for inherited diseases/syndromes affecting visual function.

Molecular characterization of the murine neural retina leucine zipper gene, Nrl.

The NRL gene (D14S46E) is expressed in cells of human retina and encodes a putative DNA-binding protein of the leucine zipper family. Here we describe the analysis of the murine homolog of the NRL gene, Nrl. Various cDNAs resulting from alternate polyadenylation are characterized. The deduced polypeptide sequence is highly conserved between mouse and human, with an identical basic motif and leucine zipper domain. The nucleotide sequences in the 5' and 3'-untranslated regions also show significant homology. The 3'-untranslated region contains a polymorphic AGG-trinucleotide repeat. The murine Nrl gene consists of three exons; of these, the first is untranslated. The 5'-upstream promoter region has no canonical TATA box, but contains consensus binding site sequences for several DNA-binding proteins. Analysis of RNA from adult mouse tissues confirms the retina-specific expression of Nrl. This study provides the basis for dissecting the cis-regulatory elements involved in the retina-specific expression and for the development of an experimental model to investigate the function or any diseases associated with this gene in humans.