Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome.

OBJECTIVE: Axenfeld-Rieger syndrome (ARS) is phenotypically and genetically heterogeneous. In this study, we identified the underlying genetic defect in a Chinese family with ARS. METHODS: A detailed family history and clinical data were recorded. The ocular phenotype was documented using slit-lamp photography and systemic anomalies were also documented where available. The genomic DNA was extracted from peripheral blood leukocytes. All coding exons and intron-exon junctions of paired-like homeodomain transcription factor 2 (PITX2) gene and the forkhead box C1 (FOXC1) gene were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Variations detected in exon 5 of PITX2 were further evaluated with cloning sequencing. The exon 5 of PITX2 was also sequenced in 100 healthy controls, unrelated to the family, for comparison. Structural models of the wild type and mutant homeodomain of PITX2 were investigated by SWISS-MODEL. RESULTS: Affected individuals exhibited variable ocular phenotypes, whereas the systemic anomalies were similar. After direct sequencing and cloning sequencing, a heterozygous deletion/insertion mutation c.198_201delinsTTTCT (p.M66Ifs*133) was revealed in exon 5 of PITX2. This mutation co-segregated with all affected individuals in the family and was not found either in unaffected family members or in 100 unrelated controls. CONCLUSIONS: We detected a novel frameshift mutation p.M66Ifs*133 in PITX2 in a Chinese family with ARS. Although PITX2 mutations and polymorphisms have been reported from various ethnic groups, we report for the first time the identification of a novel deletion/insertion mutation that causes frameshift mutation in the homeodomain of PITX2 protein.

[Clinical investigation of medication adherence of glaucoma patients].

OBJECTIVE: To investigate the medication adherence and modulation factors of medication adherence in long-term treated glaucoma patients. METHODS: It was a cross-sectional study. One hundred glaucoma patients who have been followed-up for more than 6 month in the Second Hospital affiliated to Medical College of Zhejiang University were investigated with questionnaires and interview. The data was analyzed by binary logistic regression and χ(2) test. RESULTS: In the 100 glaucoma patients being investigated, the medication compliance of patients is 61(61.0%), the medication non-compliance of patients is 39 (39.0%). Age, gender, habitat, glaucoma types, surgical history, ingesting patient before writing out a prescription and informing them the methods for application of eyedrops were not significantly co-related with medication adherence (χ(2) = 0.718, 0.537, 0.338, 3.797, 0.338, 0.297, 0.157; P > 0.05). Intraocular pressure before treatment, types of eyedrops, instillation of eye-drops to the eyelids, request for help during application of eyedrops, rechecking regularly and confidence in glaucoma treatment were found significantly related to medication adherence (P = 0.013, 0.005, 0.005, 0.012, 0.011, 0.004). However, drug side effect, forgetting application of eyedrops and inconvenience to see a doctor was considered the most important factors by patients in the interview. CONCLUSIONS: Glaucoma physicians should discuss with patients about the methods for the application of glaucoma medication. This can improve the medication adherence of glaucoma patients and promote the therapeutic effect.

[Therapeutic effect of laser photocoagulation of ciliary processes in aphakic glaucoma].

OBJECTIVE: To evaluate the therapeutic effect of laser photocoagulation of ciliary processes after pars plana vitrectomy in aphakic glaucoma. METHODS: Twenty patients (20 eyes) of aphakic glaucoma underwent vitrectomy plus laser treatment. During the surgery, after conventional 3-incision pars plana vitrectomy, a probe of semi-conductor diode laser (532 nm) was inserted through the sclera incision, the ciliary processes were then photocoagulated under direct visualization for 180 degree range. Before and after the surgery, the visual acuity, the intraocular pressure (IOP) as well as the outer appearance of the anterior segment were evaluated. The mean follow-up period was 13 months. RESULTS: The IOP at the last visit was (21.35 +/-2.52) mmHg, which was significantly lower than that before the surgery [(39.75 +/-6.27) mmHg, P=0.000]. Atrophy of the ciliary processes was observed 1-3 months after the surgery. CONCLUSION: Pars plana vitrectomy combined with laser coagulation of ciliary processes reduces the IOP in patients with aphakic glaucoma effectively.

[Indocyanine green and fluorescein angiography study of glaucomatous peripapillary atrophy].

OBJECTIVE: To investigate the incidence of glaucomatous peripapillary atrophy (PPA) and choroidal circulation of glaucomatous patients. METHODS: The subjects of glaucoma groups included 43 (43 eyes) glaucomatous patients including 16 (16 eyes) chronic angle-closure glaucoma (CACG), 27 (27 eyes) open-angle glaucoma. Control group included 33 (33 eyes) cases. Indocyanine green angiography and fundus fluorescein angiography were performed on glaucoma groups and control group with Heidelberg retinal angiography (HRA) to observe alpha zone and beta zone of PPA. RESULTS: The frequency of beta zone in CACG, open-angle glaucoma and control group was 31.3%, 77.8% and 21.9%, respectively, with statistically significant difference between these groups (chi(2) = 19.915, P = 0.000). Beta zone showed ICG hypofluorescence in all eyes. There were no statistically significant difference in the frequency of alpha zone between glaucoma groups and control group. However, there were two different types of indocyanine green filling in alpha zone: normal or decreased choroid filling. Decreased choroid filling in alpha zone was observed in 53.8% of eyes with chronic angle-closure glaucoma, 66.7% of open-angle glaucoma and 32.1% of in control, the difference was significant (chi(2) = 6.648, P = 0.036). CONCLUSIONS: The frequency of zone beta with no choroidal filling in open-angle glaucoma group is the highest among these three groups. Zone alpha in glaucomatous eyes show decreased choroidal circulation, which may be the early sign for the extension of beta zone.

[Treatment of open angle glaucoma with deep sclerectomy combined with laser trabecular puncture].

OBJECTIVE: To study the effect of deep sclerectomy combined with laser trabecular puncture for the treatment of open angle glaucoma (OAG). METHODS: Deep sclerectomy was performed in 32 eyes of 32 patients with moderate to advanced stages of OAG. After the exposure of external wall of Schlemm's canal and the remaining trabecula, the intraocular optic fiber of diode laser photocoagulator was directed to the trabecula-limbus near the anterior edge of the scleral spur. Two or three punctures, approximately 0.5 mm in diameter, were performed with laser beam under direct visualization until aqueous humor was extravasated slowly. The scleral flap was closed with one or two sutures. Postoperative observation included intraocular pressure (IOP), intraocular tissue reaction, the appearance of filtering bleb, gonioscopy and ultrasound biomicroscopy. The follow-up period was 4 to 24 months (7.94 +/- 6.20) months. RESULTS: The anterior chamber was recovered shortly after the operation and the visual acuity remained the same in all eyes. At the end of follow-up period, the postoperative IOP (14.86 +/- 4.15) mm Hg was lower than the preoperative IOP (29.68 +/- 5.76) mm Hg, the difference was statistically significant (t = 7.415, P < 0.001). Diffuse and obvious filtering blebs were found in all eyes after the operation, including 27 functional blebs and 5 blebs that disappeared 2 to 3 months later. Iris was burned slightly in 2 cases, pigment was released and appeared in the anterior chamber temporarily. No laser injury occurred in the cornea and the lens. High IOP was found in 2 cases after long-term follow-up and could be controlled by antiglaucoma medication. CONCLUSIONS: Deep sclerectomy with laser trabecular puncture can effectively reduce the IOP, without the occurrence of serious complications that commonly seen after the trabeculectomy. It is an effective surgical method for the treatment of OAG.