Thicker Inner Nuclear Layer as a Predictor of Glaucoma Progression and the Impact of Intraocular Pressure Fluctuation.

Background: Thickening of the inner nuclear layer (INL) or microcystic macular changes has been reported to be implicated in glaucoma patients, but their potential impact on disease progression remains unclear. We investigated the relationship between baseline microcystic macular edema in the INL or INL thickness and subsequent visual field (VF) progression in glaucoma patients. Methods: This retrospective observational study included primary open-angle glaucoma with follow-up exceeding 3 years. We identified macular cystic changes through Spectralis optical coherence tomography and measured the INL thickness using automated segmentation. Glaucoma progression was determined using the Guided Progression Analysis program of the Humphrey filed analyzer, calculating the mean deviation (MD) changes (dB/year). Results: Microcystic macular changes were observed in 12 (7.5%) of 162 patients. Patients with microcystic macular change had thicker INL thickness than those without it (p = 0.010). Progressors had a higher probability of having microcystic macular changes and a thicker average INL thickness than nonprogressors (p = 0.003, p = 0.019). Thicker INL thickness was associated with faster VF progression based on MD slope (dB/year) in the multivariate regression analysis (p = 0.045). Additionally, greater intraocular pressure (IOP) fluctuation was found to be associated with both a thicker INL and the presence of microcystic changes in the multivariate regression analysis (p = 0.003, 0.028). Conclusions: Increased macular INL thickness indicative of INL changes was linked to subsequent VF progression in glaucoma patients. These findings suggest that retinal inner nuclear change could serve as an indicator of progressive glaucoma.

Clinical Characteristics and Associated Factors to the Development of Glaucoma in Eyes With Myopic Optic Neuropathy.

PURPOSE: To observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage. DESIGN: A prospective, observational, cohort study. METHODS: A total of 233 myopic eyes with no definite evidence of glaucomatous damage were included. Myopic patients without any retinal nerve fiber layer (RNFL) or visual field (VF) abnormalities were classified as myopic eyes without MON. Myopic patients with decreased RNFL at the superonasal (SN) or nasal area, and with corresponding VF defects either in the temporal or inferotemporal (IT) region were classified as myopic eyes with MON. Myopic eyes that developed glaucoma were defined by the presence of glaucomatous VF in the SN region including defects in Bjerrum area, or a new localized RNFL defect in the IT region. Disc morphological features and optic nerve head (ONH) parameters of two groups were compared. RESULTS: Myopic eyes with MON had a thinner average peripapillary RNFL thickness (P < 0.001), worse MD of the VF (P = 0.031), a higher percentage of IT VF defects (P < 0.001), smaller torsion degree (P = 0.047), and greater LCD (P = 0.022). Myopic eyes with MON who developed glaucoma had a thinner average peripapillary RNFL thickness (P = 0.009), greater PPA area (P = 0.049), greater LCD (P < 0.001), and thinner LCT (P < 0.001). Thinner baseline temporal RNFL thickness (HR, 0.956; 95% CI, 0.928-0.986; P = 0.004), greater baseline LCD (HR, 1.003; 95% CI, 1.000-1.005; P = 0.022), and greater PPA area (HR, 1.000; 95% CI, 1.000-1.003; P = 0.050) were significantly associated factors with glaucoma development. CONCLUSIONS: Myopic eyes with MON have a greater risk to develop glaucoma compared to myopic eyes without MON. Structural weakness due to myopia, especially at the temporal side of the ONH and the peripapillary sclera, increases the risk of glaucoma in myopic eyes with MON.

Effect of a Pericardium Graft Inserted Adjacent to the Endplate in the Ahmed Glaucoma Valve Implantation.

The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon's space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.

Simultaneously performed combined 24-2 and 10-2 visual field tests in glaucoma.

Using either 24-2 or 10-2 visual field (VF) testing only is not enough to cover all the various types of glaucomatous VF defects. We investigated the performance of the combined 24-2 and 10-2 perimetry when conducted together and separately using the structure-function relationship. A total of 30 glaucoma patients with isolated peripheral nasal step, 37 patients with isolated paracentral scotoma, and 38 patients with both paracentral and nasal scotoma were included. To create the combined Humphrey VF test, a custom test pattern was established using the built-in custom point options, an example of the X, Y coordinate system. In glaucoma patients with peripheral nasal step, the superotemporal topographic structure-function relationship with peripapillary retinal nerve fiber layer (RNFL) thickness was superior in relation to the combined or 24-2 perimetry relative to the 10-2 perimetry (both P < 0.05). The combined VF test showed more favorable inferotemporal or inferonasal structure-function correlation with the corresponding ganglion cell-inner plexiform layer (GCIPL) thickness when compared with results gleaned using the 24-2 VF test (P < 0.05). Simultaneously performed 24-2 and 10-2 VF tests demonstrated a superior topographic structure-function relationship when compared with them separately performed in some sectors.

Retinoid production using metabolically engineered Escherichia coli with a two-phase culture system.

BACKGROUND: Retinoids are lipophilic isoprenoids composed of a cyclic group and a linear chain with a hydrophilic end group. These compounds include retinol, retinal, retinoic acid, retinyl esters, and various derivatives of these structures. Retinoids are used as cosmetic agents and effective pharmaceuticals for skin diseases. Retinal, an immediate precursor of retinoids, is derived by ß-carotene 15,15'-mono(di)oxygenase (BCM(D)O) from ß-carotene, which is synthesized from the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Retinoids are chemically unstable and biologically degraded via retinoic acid. Although extensive studies have been performed on the microbial production of carotenoids, retinoid production using microbial metabolic engineering has not been reported. Here, we report retinoid production using engineered Escherichia coli that express exogenous BCM(D)O and the mevalonate (MVA) pathway for the building blocks synthesis in combination with a two-phase culture system using a dodecane overlay. RESULTS: Among the BCM(D)O tested in E. coli, the synthetic retinoid synthesis protein (SR), based on bacteriorhodopsin-related protein-like homolog (Blh) of the uncultured marine bacteria 66A03, showed the highest ß-carotene cleavage activity with no residual intracellular ß-carotene. By introducing the exogenous MVA pathway, 8.7 mg/L of retinal was produced, which is 4-fold higher production than that of augmenting the MEP pathway (dxs overexpression). There was a large gap between retinal production and ß-carotene consumption using the exogenous MVA pathway; therefore, the retinal derivatives were analyzed. The derivatives, except for retinoic acid, that formed were identified, and the levels of retinal, retinol, and retinyl acetate were measured. Amounts as high as 95 mg/L retinoids were obtained from engineered E. coli DH5α harboring the synthetic SR gene and the exogenous MVA pathway in addition to dxs overexpression, which were cultured at 29°C for 72 hours with 2YT medium containing 2.0% (w/v) glycerol as the main carbon source. However, a significant level of intracellular degradation of the retinoids was also observed in the culture. To prevent degradation of the intracellular retinoids through in situ extraction from the cells, a two-phase culture system with dodecane was used. The highest level of retinoid production (136 mg/L) was obtained after 72 hours with 5 mL of dodecane overlaid on a 5 mL culture. CONCLUSIONS: In this study, we successfully produced 136 mg/L retinoids, which were composed of 67 mg/L retinal, 54 mg/L retinol, and 15 mg/L retinyl acetate, using a two-phase culture system with dodecane, which produced 68-fold more retinoids than the initial level of production (2.2 mg/L). Our results demonstrate the potential use of E. coli as a promising microbial cell factory for retinoid production.