Safety profile of 0.0015% tafluprost eye drops in China: a post-marketing observational study.

AIM: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China. METHODS: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected. RESULTS: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), ß-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500). CONCLUSION: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances.

Evaluation of the learning curve of laser peripheral iridectomy: the 20th case reaches the turning point.

AIM: To explore the learning curve for ophthalmologists at the start of laser peripheral iridectomy (LPI) training. METHODS: The learning curve of 4 doctor groups without previous LPI experience was studied. Three main parameters of LPI were reviewed: total energy, argon energy and neodymium-doped yttrium aluminum garnet (Nd:YAG) energy. Procedures were evaluated in cohorts of 20 cases to identify the turning points of the three variables. RESULTS: There was no significant difference in terms of age or eye among the 4 doctor groups. There were stable trends on the learning curve for the Doctor A and C groups regarding total energy and argon energy. In addition, the turning points on the learning curve were determined after the 20th procedure for the Doctor B and D groups regarding total energy and argon energy. Moreover, the Nd:YAG energy was relatively stable since the first procedure. CONCLUSION: It requires approximately 20 procedures for a beginner to reach a turning point on the learning curve regarding LPI. It can serve as a point of reference or guideline for training beginners to perform LPI.

Efficacy of autologous conjunctival flap on repairing the late-onset filtering bleb leakage.

AIM: To evaluate the effectiveness of autologous conjunctival flap surgery for repairing the late-onset filtering bleb leakage after trabeculectomy. METHODS: This study retrospectively reviewed 106 eyes from 106 patients with late-onset filtering bleb leakage after trabeculectomy who received autologous conjunctival flap surgery at the Zhongshan Ophthalmic Centre from 2005 to 2015. The basic information was recorded, and the interval time between trabeculectomy and autologous conjunctival flap surgery as well as related risk factors, intraocular pressure (IOP), anterior chamber depth (ACD) and best corrected visual acuity (BCVA) were analysed. Moreover, 41 patients who completed the 1-year follow up were analysed to determine the IOP and BCVA changes and long-term success rates. RESULTS: The 50 male and 56 female subjects (average age 39.13±17.96y) included 47 (44.34%) and 33 (31.13%) cases of primary open angle and primary angle-closure glaucoma. The mean interval between trabeculectomy and repair surgery was 60.60±56.92 (3-264)mo. The mean mitomycin (MMC) concentration during trabeculectomy was 0.27±0.04 (0.12-0.4) mg/mL in the fornix-based conjunctival flap group (68 patients) and 0.28±0.04 (0.20-0.33) mg/mL in the limbal-based conjunctival flap group (11 patients). After bleb leakage, the patients' vision remained stable while the IOP decreased from 10.25±4.76 (3-20.86) to 9.44±4.33 (2-21) mm Hg (P<0.01). In the 41 analysed patients, the IOP was controlled at 15.68±5.11 (7-40) mm Hg in the 1st year after autologous conjunctival flap surgery and recurrence was not observed, for a long-term success rate of 100%. CONCLUSION: Autologous conjunctival flap repairing surgery is an effective technique for sealing filtering bleb leakages and controlling IOP postoperatively.

Comparison of combined phacotrabeculectomy with trabeculectomy only in the treatment of primary angle-closure glaucoma.

BACKGROUND: Trabeculectomy has become a mainstream treatment in intraocular pressure (IOP) reduction for primary angle-closure glaucoma (PACG); combined trabeculectomy and cataract surgery was reported to reduce IOP and simultaneously improve vision for patients with PACG and coexisting cataract. This study was specialized to compare the efficacy and safety of combined phacotrabeculectomy with that of trabeculectomy only in the treatment of PACG with coexisting cataract. METHODS: This is a comparative case series study. Thirty-one patients (31 eyes) with PACG and coexisting cataract were enrolled. Of these, 17 underwent phacotrabeculectomy and 14 underwent trabeculectomy alone. IOP, filtering blebs, and complications were compared at the final follow-up. Complete success was defined as a final IOP less than 21 mmHg without IOP-lowering medication. RESULTS: After 10 months of postoperative follow-up, the phacotrabeculectomy and trabeculectomy groups showed no significant differences regarding IOP reduction ((20.59 ± 7.94) vs. (24.85 ± 14.39) mmHg, P = 0.614), complete success rate (88% vs. 71%, P = 0.370), formation rate of functioning blebs (65% (11/17) vs. 93% (13/14), P = 0.094), and complications (41% (7/17) vs. 57% (8/14), P = 0.380). IOP-lowering medication was not required for most of the patients in both groups. Additional surgery interventions, including anterior chamber reformation and phacoemulsification, were needed in the trabeculectomy group, whereas no surgery was needed postoperatively in the phacotrabeculectomy group. CONCLUSION: Phacotrabeculectomy and trabeculectomy treatments exhibit similar IOP reduction, successful rates, and complications when it comes to treating PACG patients with coexisting cataract, although additional surgery intervention may be needed for a few cases with cataract and complications after trabeculectomy.

[The blood-aqueous barrier changes after laser peripheral iridotomy or surgery peripheral iridectomy].

OBJECTIVE: To investigate the ocular blood-aqueous barrier (BAB) alteration after laser peripheral iridotomy (LPI) or surgery peripheral iridectomy (SPI) in patients with primary chronic angle-closure glaucoma (PCACG). METHODS: This was a clinical randomized controlled trial. Sixty eyes of 60 subjects with early stage of PCACG were randomly received either LPI or SPI and followed up postoperatively at day 3, week 1, 2, 3, and 4. Aqueous flare in anterior chamber was measured by FC-2000 flare-cell photometry, intraocular pressure (IOP) measured by tonometer, central corneal endothelium cell counted by endothelioscopy, peripheral anterior synechiae (PAS) detected by gonioscopy. Data were analyzed by using two-way ANOVA for repeated measures, independent samples t-test, paired t-test, nonparametric test, and Spearman rank correlation test. RESULTS: On follow-ups of pre-operative and post-operative 3 days, 1 week (w), 2w, 3w and 4w respectively, the mean aqueous flare values for LPI group were (5.47 ± 1.09), (11.96 ± 3.07), (8.08 ± 2.18), (5.68 ± 0.83), (5.80 ± 1.00), (5.69 ± 1.12) PC/ms, and for SPI group were (5.43 ± 1.13), (8.44 ± 3.22), (6.42 ± 1.77), (5.35 ± 0.71), (5.53 ± 1.26), (5.45 ± 1.23) PC/ms. During post-operative 1w the flare values in both LPI and SPI groups were significantly higher than that on pre-operation (t = -12.753, -8.101, P < 0.05; t = -5.971, -3.870;P < 0.05) and LPI group had a significantly higher mean flare value than SPI group (t = 4.329, 3.231;P < 0.05). The IOP spike in LPI group was significantly (χ(2) = 5.079, 4.022, P < 0.05) higher than that in SPI group at week 1 of post-operation. Increased IOP was positively correlated with BAB damage (r = 0.899, 0.833; P < 0.05). The numbers of medications required to maintain IOP ≤ 21 mm Hg (1 mm Hg = 0.133 kPa) at week 4 of post-operation in LPI was significantly (Z = -1.984, P < 0.05) more than that in SPI group. There were no significant differences in central corneal endothelium cell count at week 1 (t = -0.696, 0.008) and in extension of PAS at week 4 (Z = -1.270, -1.490) of post-operation when compared to pre-operation (P > 0.05). No obvious complications occurred in both groups. CONCLUSIONS: Our results demonstrated that IOP spike in both of LPI and SPI is due, at least in part, to BAB damage, which appears to be more severe in LPI group and can recover within two weeks. PAS progression and central corneal endothelium cell loss are not aggravated in 1 month after operation.

[Long-term effects of non-penetrating trabecular surgery versus trabeculectomy for treating glaucoma].

OBJECTIVE: To evaluate clinical outcomes of non-penetrating trabecular surgery (NPTS) and trabeculectomy surgery (TS) in the treatment of primary open angle glaucoma (POAG). METHODS: It was a case-control study. A total of 63 patients (63 eyes) with POAG were observed retrospectively. Thirty one eyes and 32 eyes underwent NPTS and TS, respectively. Intraocular pressure (IOP), filtration bleb, visual field and post-operative complications were observed for 6-60 months. The CMH χ(2) test was used to analyse the difference of them. RESULTS: After operation, the IOP in the NPTS group were from (13.87 ± 4.88) mm Hg (1 mm Hg = 0.133 kPa) to (24.01 ± 6.55) mm Hg, the IOP in the TS group were from (11.90 ± 4.92) mm Hg to (19.10 ± 7.43) mm Hg. The IOP in the NPTS group was significantly higher than that in the TS group (F = 5.137, P < 0.05). The ratio of sustained filtration bleb of NPTS group after surgery was 25/31 (80.6%), while 6/31 were flat filtration bleb. There were statistically significant difference in the rate of disappearance of filtration bleb between these two groups (χ(2) = 8.129, P < 0.05). The difference of visual field loss postoperatively between these two groups was not statistically significant. The incidence rate of newly developed cataract after NPTS and TS was 6/31 and 12/32, respectively. The difference of rate of complication between these two groups was statistically non-significant (χ(2) = 3.797, P < 0.05). The successful rate after NPTS and TS was 61.54% (16/26) and 14.29% (4/28), respectively. The difference of successful rate between these two groups was statistically significant (χ(2) = 14.463, P < 0.05). CONCLUSIONS: Both NPTS and TS are effective methods for the treatment of POAG. Postoperative complications after NPTS are less than those of TS, But patients with TS could maintain a lower IOP than those with NPTS. Long-term efficacy of NPTS is uncertain, it's important to choose the suitable surgery to gain a high success rate.

[Gene screening as the forewarning measure to predict glaucoma].

OBJECTIVE: To investigate the effect of gene screening on forewarning and monitoring of familial open-angle glaucoma pedigree. METHODS: Comprehensive ophthalmic examinations were performed in all available family members. The genomic DNA was extracted from peripheral blood. The myocilin gene was amplified and screened for mutations using direct sequencing. All family members were followed up. RESULTS: Among 12 family members, 5 individuals carry a C to T transition in exon 3 resulting in the substitution of proline to leucine (Pro370Leu), and the other 7 individuals did not carry this mutation. Ophthalmic examinations did not show any abnormality in the optic disc, the thickness of RNFL, and visual field parameters in mutation-carriers. During the follow-up, all carriers were diagnosed as open-angle glaucoma. The mean time of presentation of the defect of visual field was 21.6 months and 14.4 months after the changes in RNFL thickness. CONCLUSION: Genetic diagnosis was proven to be a method with high specificity and sensitivity; and can be used for presymptom diagnosis and forewarning in familial open-angle glaucoma pedigree.

[Clinical observation of trabeculectomy for primary angle closure glaucoma].

OBJECTIVE: To evaluate the effect of trabeculectomy on intraocular pressure (IOP) and complications in eyes with primary angle closure glaucoma (PACG). METHODS: It was retrospective clinical study. PACG was classified as acute primary angle closure glaucoma (APACG) group and chronic primary angle closure glaucoma (CPACG) group. APACG was then divided into acute attack phase and chronic phase, and CPACG was divided into chronic phase and late phase. IOP, best corrected visual acuity were compared before and after trabeculectomy in different subgroup of PACG. In addition, the incidence of complications of trabeculectomy was assessed. Statistical analyses were performed using SPSS 12.0 statistics software. Categorical variables such as best corrected visual acuity were compared using nonparametric test, continuous variables such as age and IOP were compared between the two groups using independent two-sample t-tests. Pre- and postoperative IOP were compared using one-way analysis of variance of repeated measures. RESULTS: 40 eyes (37 cases) of APACG and 56 eyes (45 cases) of CPACG were enrolled in this study. The median follow-up period was 24 and 25 months, respectively. IOP was significantly decreased from (53.6 +/- 17.9) mm Hg (1 mm Hg = 0.133 kPa, preoperation) to (10.5 +/- 4.9) mm Hg (postoperation) at time of discharging from hospital and (14.0 +/- 10.3) mm Hg at time of final follow up in APACG (F = 100.783, P < 0.01), respectively, and from (36.8 +/- 13.8) mm Hg to (11.7 +/- 4.2) mm Hg at time of discharging from hospital and (13.8 +/- 4.5) mm Hg at time of final follow up in CPACG (F = 54.383, P < 0.01), respectively. The IOP remained controlled (< or = 21 mm Hg) without antiglaucomatous medication in 38 eyes (95.0%) of APACG and in 50 eyes (89.3%) of CPACG. Visual acuity was significantly (H = 12.316, P < 0.01) decreased after trabeculectomy in all sub-types of PACG by Kruskal-wallis analysis. Shallow anterior chamber was commonly occurred after trabeculectomy. CONCLUSIONS: Trabeculectomy is an effective method to control IOP in APACG and CPACG. However, the high proportion of impaired vision was found following trabeculectomy in this study and warranted further clinical investigation.

[The efficacy of surgical treatment for encapsulated cystic blebs around the plate after Ahmed glaucoma valve implantation].

OBJECTIVE: To evaluate the efficacy of surgical treatment for encapsulated cystic blebs around the plate after Ahmed glaucoma valve implantation. METHODS: This was a retrospective observational case series. Thirteen cases with elevated intraocular pressure (IOP) induced by fibrous proliferation around Ahmed valve were retrospectively studied. The intraocular pressure increased at 3 weeks to 5 months post-operation (2 months in average). The plates and tubes of Ahmed valve were in good position. No obstruction was seen in the tubes. Localized, encapsulated, cystic blebs were found in the equator of eyeball in which the plates were located. All cases underwent encapsulated cysts resection combined with mitomycin-C usage under conjunctival flaps. The excised tissues were sent for pathological examination. The changes of IOP and the outcome of the diseases were observed. RESULTS: IOP was normal one month after surgery in all cases. The success rate was 100%. In the 3 - 20 months follow-up period, the IOP level kept normal in 3 cases without any anti-glaucoma medications. The IOP level was in normal range in 6 cases using two or three different kinds of anti-glaucoma medications. Three cases needed further surgical treatment because of uncontrolled IOP even with anti-glaucoma medications. Among them, the complete success rate was 75% (3/4) in patients more than 57 years old, while the complete success rate was 0 (0/8) in patients less than 37 years old. CONCLUSIONS: It was considered an effective method of surgical treatment for encapsulated blebs around Ahmed glaucoma valve. The result was better in elderly patients than in younger patients relatively.

Pro370Leu MYOC gene mutation in a large Chinese family with juvenile-onset open angle glaucoma: correlation between genotype and phenotype.

PURPOSE: Glaucoma is the leading cause of irreversible blindness worldwide. Most of the cases are primary open angle glaucoma (POAG). POAG is a genetically heterogenous disease; autosomal dominance is the most frequent type of monogenic inheritance. In this study, we identified the genotype of a MYOC mutation and investigated the phenotype of a Chinese juvenile-onset open angle glaucoma (JOAG) pedigree (GZ.1 pedigree). METHODS: Blood samples were obtained from 24 participants. We performed sequence and gene linkage analysis in the GZ.1 pedigree retrospectively. Comprehensive ophthalmologic examinations were performed for each family member. Pharmacological treatment or filtering surgery was performed as needed according to the intraocular pressure (IOP) of each individual. RESULTS: A Pro370Leu myocilin mutation located in exon 3 of MYOC was identified in 24 members of the GZ.1 pedigree. Sixteen patients had juvenile-onset primary open-angle glaucoma (JOAG), and the others participating in the project had no such genotype. Analysis of polymorphic microsatellite markers indicated that the disease in GZ.1 is autosomal dominant inheritance. The patients in GZ.1 are characterized by early age of onset (before 35 years of age), severe clinical presentations, and high intraocular pressure unresponsive to pharmacological treatment; requiring 89.5% of the patients to undergo filtering surgery. Fortunately, the success rate of surgery was high. None of the patients required further medical treatment and only one demonstrated low IOP fundus changes. CONCLUSIONS: This is the first evidence of a founder effect for a Pro370Leu myocilin mutation in a Chinese POAG pedigree. The family with the Pro370Leu myocilin mutation presents with juvenile-onset glaucoma. After 10 years of follow-up, it is evident that the mutation is closely associated with the phenotype of the patients. Analysis of MYOC in JOAG patients may enable the identification of at-risk individuals and help prevent disease progression toward the degeneration of the optic nerve, and may also contribute to genetic counseling.

[Experimental study on the effects of interferon-gamma gene on Tenon's capsule fibroblasts in vitro].

OBJECTIVE: To investigate the effects of interferon-gamma (IFN-gamma) gene on Tenon's capsule fibroblasts in vitro. METHODS: Using lipofectAMINE, IFN-gamma gene was transferred to human Tenon's capsule fibroblasts with plasmid pcDNA3IFN-gamma in vitro. Cells treated with plasmid pcDNA3 without IFN-gamma gene were used as the controls. The transfected fibroblasts were screened by G418. The expression of IFN-gamma was determined by RT-PCR, immunohistochemistry and flow cytometry assay. The effects of IFN-gamma on the proliferation of Tenon's capsule fibroblasts were evaluated by flow cytometry and MTT. RESULTS: The Tenon's capsule fibroblasts transferred the IFN-gamma gene could express the IFN-gamma RNA and protein transiently. The proliferation of the fibroblasts transferred the IFN-gamma gene was inhibited. CONCLUSION: The proliferation of the Tenon's capsule fibroblasts in vitro can be inhibited by transferred IFN-gamma gene.

[A preliminary study on gene mutation and its function in a large family (GZ.1 pedigree) with open-angle glaucoma].

OBJECTIVE: To determine the causative mutation of myocilin gene and to investigate its pathogenic function in a large Chinese pedigree (GZ.1) with familial open-angle glaucoma. METHODS: Genome-wide scanning was performed and the Lod scores were calculated. Candidate gene was amplified and screened for mutations using direct sequencing. To elucidate its expression, distribution and cytotoxicity of mutant myocilin, human trabecular cells (HTM) cells were transfected with pcDNA-wild-type and mutant myocilin vectors using liposomes. RESULTS: Mutation analysis of the myocilin gene showed a C-to-T transition at the 1, 109 th nucleotide in exon 3 resulting in a change of amino acid from proline to leucine (Pro370Leu). This mutation cosegregated with all affected individuals (16/16) and never presented in unaffected individuals (0/8). In transfected HTM cells, the mutant myocilin protein was not correctly processed in ER and accumulated as aggresome-like structures in the cytoplasma instead of being secreted. In addition, the expression of mutant protein also led to apoptosis of trabecular cells and the occurrence of. CONCLUSION: The mutation of Pro370Leu in myocilin gene could cause the accumulation of misfolding myocilin protein in HTM cells, which might lead to glaucoma in GZ.1 pedigree.

[The inhibition effect of photodynamic on human Tenon capsule fibroblast cells].

OBJECTIVE: To investigate the inhibition of photodynamic effect on human Tenon capsule fibroblast cells in vitro. METHODS: The human Tenon capsule fibroblast cells were divided into nine groups named as group A to I, each group had four wells. Group A to G, each group was added photosensitizer benzoporphyrin derivative monoacid ring A (BPD) with end concentration of 2.50 x 10(3) g/L, 1.25 x 10(3) g/L, 0.62 x 10(3) g/L, 0.31 x 10(3) g/L, 0.16 x 10(3) g/L, 0.08 x 10(3) g/L, 0.04 x 10(3) g/L respectively. Then the culture cells were irradiated by 689 nm diode laser with dosage of 2.4 J/cm(2) after BPD treatment for 15 minutes. Group H was treated with Mitomycin C (MMC) at concentration of 0.2 g/L. Group I was control without any treatment. All the cells were kept cultured for another 24 hours and then MTT colorimetric assay was applied to measure the relative inhibitory rate of photodynamic effect on the cells. RESULTS: There is statistical significance between group A to H and group I with the method of one way analysis of variance. When compared to group I, the relative inhibitory rates of group A to G are 93.3%, 91.0%, 90.3%, 87.1%, 66.0%, 41.6%, 12.5% respectively, and the inhibitory rate of group H (MMC) is 93.0%. CONCLUSION: Photodynamic effect can inhibit the proliferation of human Tenon capsule fibroblast cells in vitro. The inhibitory rate appears to be dependent on the concentration of the photo sensitizer.