Gonioscopy-assisted transluminal trabeculotomy for open-angle glaucoma with failed incisional glaucoma surgery: two-year results.

BACKGROUND: To evaluate the safety and efficacy of gonioscopy-assisted transluminal trabeculotomy (GATT) in treating patients with open-angle glaucoma (OAG) who had failed prior incisional glaucoma surgery. METHODS: A consecutive case series of OAG patients aged ≥ 18 who underwent GATT with previous failed glaucoma incision surgery was retrospectively analyzed. Main outcome measures included intraocular pressure (IOP), the number of glaucoma medications, surgical success rate, and occurrence of complications. Success was defined as an IOP of ≤ 21 mmHg and a reduction of IOP by 20% or more from baseline with (qualified success) or without (complete success) glaucoma medications. For eyes with preoperative IOP of < 21 mmHg on 3 or 4 glaucoma medications, postoperative IOP of ≤ 18 mmHg without any glaucoma medications was also defined as complete success. RESULTS: Forty-four eyes of 35 patients (21 with juvenile-onset open-angle glaucoma and 14 with adult-onset primary open-angle glaucoma) with a median age of 38 years were included in this study. The proportion of eyes with 1 prior incisional glaucoma surgery was 79.5%, and the others had 2 prior surgeries. IOP decreased from 27.4 ± 8.8 mm Hg on 3.6 ± 0.7 medications preoperatively to 15.3 ± 2.7 mm Hg on 0.5 ± 0.9 medications at the 24-month visit (P < 0.001). The mean IOP and the number of glaucoma medications at each follow-up visit were lower than the baseline (all P < 0.001). At 24 months postoperatively, 82.1% of the eyes had IOP ≤ 18 mmHg (versus 15.9% preoperatively, P < 0.001), 56.4% reached IOP ≤ 15 mmHg (versus 4.6% preoperatively, P < 0.001), and 15.4% achieved IOP ≤ 12 mmHg (compared to none preoperatively, P = 0.009). While 95.5% of eyes took 3 or more medications preoperatively, 66.7% did not take glaucoma medication 24 months after GATT. Thirty-four (77.3%) eyes achieved IOP reduction greater than 20% on fewer medications. The complete and qualified success rates were 60.9% and 84.1%, respectively. No vision-threatening complications occurred. CONCLUSIONS: GATT was safe and effective in treating refractory OAG patients who failed prior incisional glaucoma surgery.

A common variant near TGFBR3 is associated with primary open angle glaucoma.

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

[Statistical model analysis of primary angle closure glaucoma associated genes and SNP].

OBJECTIVE: To evaluate GWAS significant associated SNP for primary angle closure glaucoma. METHODS: Experimental study. Taking advantage of different statistical models, the usefulness was evaluated by sensitivity, specificity and the area under the receiver-operating characteristic curve (ROC), which indicates the accuracy of genetic profiling in discriminating between primary angle closure glaucoma patients and normal controls. RESULTS: rs11024102 (PLEKHA7) had a sensitivity of 55.88% with a specificity of 51.31%; the sensitivity and specificity of rs3753841 (COL11A1) was 54.47% and 51.00% respectively. The sensitivity of rs1015213 (PCNTD1-ST18) and rs1401999 (ABCC5) were 59.93% and 52.97%. The specificity of these two SNP were 45.32% and 50.00%. The positive predictive value curves of these four SNP were nearly reference line. The area under the curve (AUC) of four SNP combined was 0.51 and 0.52 in two situations. CONCLUSION: These four GWAS significant SNP could not be used for primary angle closure glaucoma patients screening in clinic.

[The comparison of short-term outcome between aqueous drainage pathway reconstruction surgery versus canaloplasty for open angle glaucoma].

OBJECTIVE: To compare the safety and efficacy between canaloplasty and aqueous drainage pathway reconstruction surgery in patients with open-angle glaucoma (OAG). METHODS: It is a retrospective case series study. Thirty-one eyes (25 patients) with OAG were divided into canaloplasty (n = 17; 54.8%) group or aqueous drainage pathway reconstruction (n = 14; 45.2%) group. The intraocular pressure (IOP), numbers of IOP-lowering medications and incidence of complications were recorded at 1 day, 1 week, 1, 3, 6 and 12 months after the operation. Independent-samples T test was used to compare the IOP, numbers of IOP-lowering medications before and 1, 3, 6, 12, 24 months after surgery between two groups. Kaplan-Meier Survival Analysis was used to analyze the success rate of these two surgical methods. Log rank test was used to compare the difference of cumulative success rate at 6, 12 months after surgery. RESULTS: The mean IOP values were (24.7 ± 8.7) , (14.5 ± 2.5), (14.9 ± 2.5) , (14.9 ± 2.5), (14.7 ± 2.1) and (15.4 ± 2.3) mmHg (1 mmHg = 0.133 kPa) in canaloplasty group at before surgery, 1, 3, 6, 12 and 24 months after surgery. The same values were (28.5 ± 10.6), (14.3 ± 3.6), (14.2 ± 3.2), (14.3 ± 3.6), (15.9 ± 3.2) and (14.6 ± 0.7) mmHg in aqueous drainage pathway reconstruction group. There was no difference in the extent of IOP reduction between these two groups (preoperative: t = -1.1014, P = 0.278; postoperative 1 month: t = 0.696, P = 0.492;3 month: t = 0.594, P = 0.557; 6 month: t = 0.536, P = 0.596; 12 month: t = -1.127, P = 0.273; 24 month: t = 0.455, P = 0.656). There were significant differences (P < 0.01) in post-surgery IOP lowering medication usage between these two groups, while pre-surgery medication usage were similar. The incidence of hyphema was significantly lower in aqueous drainage pathway reconstruction surgery group (2 eyes) than that in canaloplasty group (11 eyes). CONCLUSIONS: Both canaloplasty and aqueous drainage pathway reconstruction could reduce IOP effectively for open-angle glaucoma. The incidence of complication was lower in the aqueous drainage pathway reconstruction group than canaloplasty group. However, long-term efficacy between these two groups is yet to be determined.

The Relationship Between Nailfold Microcirculation and Retinal Microcirculation in Healthy Subjects.

OBJECTIVE: To evaluate whether the nailfold microcirculation is associated with retinal microcirculation in healthy subjects. METHODS: Fifty subjects without systematic and ocular diseases were enrolled. Thickness of peripapillary retinal nerve fiber layer (RNFL), vessel density (VD) of radial peripapillary capillaries (RPCs), and superficial capillary VD in macular zone were measured with optical coherence tomography angiography (OCTA) in left eyes. Nailfold microcirculation, including capillary density, avascular zones, dilated capillaries, and hemorrhages was examined on the fourth digit of each subject's non-dominant (left) hand with nailfold capillaroscopy (NFC). RESULTS: After adjustment for relatively systemic factors, multivariate regression analyses showed a significant direct relationship between RNFL thickness and nailfold capillary density (OR = 1.09; p = 0.046). RNFL thickness and RPCs VD were negatively correlated with nailfold avascular zones (OR = 0.855; p = 0.007; OR = 0.596; p = 0.010). Superficial VD of parafovea was negatively associated with dilated nailfold capillaries (OR = 0.794; p = 0.012). CONCLUSION: In healthy subjects, nailfold capillary lower density and abnormalities are associated with reduced RNFL thickness and retinal VD. The results provide a theoretical foundation for relevant studies on ocular diseases with microvascular abnormalities and could contribute to pathogenesis understanding in the future. NFC and OCTA have the potential to identify risk factors and improve accuracy of the early diagnosis and treatment of ocular diseases, even systemic diseases with any microvascular component in clinical practice. CLINICAL TRAIL REGISTRATION: http://www.chictr.org.cn/index.aspx, identifier ChiCTR 1800017875.

Association of three single nucleotide polymorphisms at the SIX1-SIX6 locus with primary open angle glaucoma in the Chinese population.

This study investigated the genetic association of three single nucleotide polymorphisms (SNPs; rs10483727, rs33912345, and rs146737847) at the SIX1-SIX6 locus with primary open angle glaucoma (POAG) in the Chinese population. A total of 866 subjects with POAG (685 high-tension glaucoma (HTG) and 181 normal-tension glaucoma (NTG)) and 266 control individuals were included. Significant genetic association was identified for rs10483727 in HTG (P=0.02; odds ratio (OR)=1.31), NTG (P=7.41×10(-6); OR=2.71), and POAG (i.e., HTG and NTG combined; P=0.001; OR=1.44). rs33912345 was also significantly associated with HTG (P=0.008; OR=1.36), NTG(P=2.72×10(-6); OR=2.27), and POAG (P=3.84×10(-4); OR=1.49). The rare SIX6 mutation, rs146737847, was not found in the subjects enrolled in this study. Stratification by patient age identified that both rs10483727 and rs33912345 were significantly associated with NTG in patients aged above 40 years (P=2.08×10(-5); OR=2.28), whereas in patients aged between 20-40 years, rs33912345 was significantly associated with NTG (P=0.017; OR=2.06). In HTG, the genetic associations for both rs10483727 and rs33912345 were significant in patients aged between 20-40 years (P=0.006; OR=1.56) but not in those aged above 40 years (P=0.118, OR=1.21 and P=0.042, OR=1.29, respectively). This study replicated the association of POAG with two SNPs at the SIX1-SIX6 locus and demonstrated that SNPs, rs10483727 and rs33912345, are significantly associated with POAG, especially with NTG in patients aged above 40 years.

Pressure balance and imbalance in the optic nerve chamber: The Beijing Intracranial and Intraocular Pressure (iCOP) Study.

To determine the interdependence of intracranial pressure (ICP) and intraocular pressure (IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure (LCP), optic nerve subarachnoid space pressure (ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP (via shunting cerebrospinal fluid (CSF) from the ventricle) were recorded. At baseline, all examined pressures were different (ICP0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient (TLPG) remained stable (ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined (ICP-IOP independent zone). The optic nerve pressure gradient (ONPG) and trans-optic nerve pressure gradient (TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.

Intracranial pressure (ICP) and optic nerve subarachnoid space pressure (ONSP) correlation in the optic nerve chamber: the Beijing Intracranial and Intraocular Pressure (iCOP) study.

PURPOSE: Because a lowered intracranial pressure (ICP) is a possible mechanism of optic neuropathy, we wished to study the CSF dynamics in the optic nerve chamber by recording possible changes in the optic nerve subarachnoid space pressure (ONSP) and the impact on it when acutely lowering ICP. METHODS: In eight normal dogs pressure probes were implanted in the left brain ventricle, lumbar cistern, optic nerve subarachnoid space and in the anterior eye chamber. Following CSF shunting from the brain ventricle we monitored changes of ICP, lumbar cistern pressure (LCP), ONSP and intraocular pressure (IOP). RESULTS: At baseline, the pressures were different with ICP>LCP>ONSP but correlated with each other (P<0.001). The "trans-lamina cribrosa pressure gradient" (TLPG) was highest for IOP-ONSP, lower for IOP-LCP, and lowest for IOP-ICP (P<0.001). During CSF shunting the ICP gradually decreased in a linear fashion together with the ONSP ("ICP-depended zone"). But when the ICP fell below a critical breakpoint, ICP and ONSP became uncoupled and ONSP remained constant despite further ICP decline ("ICP-independent zone"). CONCLUSIONS: Because the parallel decline of ICP and ONSP breaks down when ICP decreases below a critical breakpoint, we interpret this as a sign of CSF communication arrest between the intracranial and optic nerve SAS. This may be caused by obstructions of either CSF inflow through the optic canal or outflow into the intra-orbital cavity. This CSF exchange arrest may be a contributing factor to optic nerve damage and the optic nerve chamber syndrome which may influence the loss of vision or its restoration.

New loci and coding variants confer risk for age-related macular degeneration in East Asians.

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys.

PURPOSE: To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS: This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve a CSF of approximately 40 mm H2O, while the shunt remained closed in the control group (n = 5 monkeys). At baseline and in monthly intervals thereafter, optical coherence tomographic and photographic images of the optic nerve head and RNFL were taken of all monkeys. RESULTS: Two out of four monkeys in the study group showed bilaterally a progressive reduction in RNFL thickness between 12% and 30%, reduction in neuroretinal rim area and volume, and increase in cup-to-disc area ratios. A third monkey developed a splinter-like disc hemorrhage in one eye. The fourth monkey in the study group did not develop morphologic changes during follow-up, nor did any monkey in the control group. CONCLUSIONS: Experimental and chronic reduction in CSF in monkeys was associated with the development of an optic neuropathy in some monkeys.