Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study.

BACKGROUND: Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population. METHODS: Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing. RESULTS: Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes. CONCLUSION: Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.

Dose, timing and frequency of subconjunctival 5-fluorouracil injections after glaucoma filtering surgery.

BACKGROUND: Although adjunctive postoperative 5-fluorouracil (5-FU) injections are known to improve the success rate of glaucoma surgery, it is still unknown what dose, timing and frequency of application will give the best results with respect to the inhibition of postoperative scarring and intraocular pressure regulation. We therefore designed the following retrospective investigation. METHODS: We studied 172 eyes from 172 patients who had undergone trabeculectomy with adjuvant 5-FU-therapy. Variations of dosage, timing and frequency were analysed retrospectively. Surgery was defined as a complete success when the patient reached an intraocular pressure under 21 mmHg and a reduction of 20% 12 months after the operation. A relative success was achieved with these criteria under additional local medication. Not reaching these postoperative criteria for a complete success was classified as failure. RESULTS: On average, adjunctive 5-FU-treatment was started 4.6+/-5.85 days postoperatively. The injections contained between 2 mg and 5 mg FU, and the mean total dose was 26.6+/-13.2 mg (range 5-65 mg). Surgery on 94 patients (54.65%) was classified as "complete success", that on 25 patients (14.53%) was classified as "relative success" and that on 53 eyes (30.81%) was classified as "failure" 12 months (+/-3 months) postoperatively. The best results were obtained when the treatment started on or before the first postoperative day (68.0-71.4% complete success; P<0.05). In contrast, an increase in 5-FU dosage did not result in an increased success rate of trabeculectomy. None of the 172 patients suffered from vision-threatening complications such as endophthalmitis or hypotony maculopathy. CONCLUSION: Early treatment with 5-FU significantly increases the success rates of filtering surgery.

Muscarinic acetylcholine receptor subtypes in human corneal epithelium and endothelium.

BACKGROUND: Muscarinic acetylcholine receptors are located throughout the body. The demonstration of muscarinic receptors in corneal tissue has been inconsistent. Using freshly fixed human corneal tissue, we show a complete profile of muscarinic receptor subtypes in human corneal epithelium and endothelium. METHODS: Muscarinic receptor sites were studied using immunocytochemistry, immunofluorescence and immunoblotting. RESULTS: Antibodies to M2, M4 and M5 muscarinic receptor subtypes bound in human corneal epithelium and endothelium. No binding was found for antibodies to M1 and M3 muscarinic receptor subtypes. CONCLUSIONS: Our studies indicate the presence of M2, M4 and M5 muscarinic acetylcholine receptor subtypes in human corneal epithelium and endothelium. These receptors may play a role in the regulation of corneal homeostasis, other functions, like wound healing, or the pathogenesis of corneal diseases.

Intraoperative breakage of 20-gauge Tano forceps.

PURPOSE: To report three cases with breakage of a 20-gauge kryptonite forceps during vitreoretinal surgery. DESIGN: Interventional case report. METHODS: Pars plana vitrectomy that included a membrane peeling was performed in three patients through standard ports with 20-gauge vitrectomy systems. The peeling procedure was attempted with the end-gripping kryptonite forceps. RESULTS: Intraoperatively, the branch/tip broke and dropped onto the posterior pole. Removal of the broken part was uncomplicated, and the subsequent clinical course was unremarkable. In one case, the handle and branch/tip part were exchanged inadvertently. In the other two cases, neither an exchange nor a maladaptation of the parts was noted. CONCLUSION: An exchange of the hand piece and gripping end may increase the risk of breakage and retinal damage. The delicate gripping tips, however, may break because of inadequate maintenance and/or aging of the material. Intraoperative visual and functional examination is recommended before intraocular use.