Association of lateral rectus muscle volume and ocular motility with the abducens nerve in Duane's retraction syndrome.

PURPOSE: To investigate the relationship between ocular motility and lateral rectus (LR) muscle volume according to the presence or absence of the abducens nerve in patients with Duane's retraction syndrome (DRS) using high-resolution magnetic resonance imaging (MRI). METHODS: A total of 54 unilateral DRS patients were divided into two groups according to high-resolution MRI findings: DRS without an abducens nerve on the affected side (absent CN6 group, n = 45) and DRS with symmetric abducens nerves on both sides (present CN6 group, n = 9). Ocular motility was measured by image analysis based on nine gaze photographs. LR volume was measured on T2-weighted coronal MRI of the orbit, and the ratio of paretic/normal side (P/N) LR volume was investigated. Association of the abducens nerve with various parameters including ocular motility, LR volume, and ratios of P/N LR volume were determined. RESULTS: LR volume was smaller in the affected eye than the non-affected eye in both groups. In the present CN6 group, abducens nerve diameter and the ratio of P/N LR volume showed a positive correlation. A smaller LR volume and more limitation of abduction in the affected eye were predictive of an absent abducens nerve in DRS. CONCLUSIONS: LR muscle hypoplasia was apparent in the affected eye of DRS patients. Abducens nerve diameter positively correlated with the ratio of P/N LR volume in the present CN6 group. Graphical abstract.

Increased CSF tau level is correlated with decreased lamina cribrosa thickness.

BACKGROUND: This study was to investigate whether the previously proposed link between Alzheimer's disease (AD) and decreased retinal nerve fiber layer thickness could be explained by the relationship between abnormal CSF profiles and optic nerve head characteristics, focusing on the influence of CSF tau protein on the lamina cribrosa (LC) thickness (LCT). METHODS: A total of 44 eyes from 18 patients with AD and 26 healthy subjects were subjected to enhanced-depth-imaging volume scanning of the optic nerve using spectral-domain optical coherence tomography. The B-scan images were constructed three-dimensionally using maximum intensity projection (MIP), and the LCT was measured at three locations (superior midperipheral, midhorizontal, and inferior midperipheral) using the thin-slab MIP images. CSF levels of amyloid ß 1-42 peptide, (Aß1-42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) were measured from CSF samples of each subject. The relationship between the level of CSF proteins and the LCT was determined using linear regression and fractional polynomial analyses. RESULTS: Univariate regression analysis revealed that higher CSF levels of T-tau (P = 0.004) and P-tau181P (P = 0.027), as well as a smaller central corneal thickness (P = 0.032), were significantly associated with a smaller LCT. Multivariate analysis indicated that only CSF T-tau (P = 0.041) was significantly associated with the LCT. The relationship was well explained by both linear regression (R(2) = 0.179, P = 0.004) and fractional polynomial analysis (R(2) = 0.275, P = 0.001). When we performed an assessment by linear regression with an indicator, the relationship was significant both in the healthy and AD groups, with a stronger correlation found in the healthy group (regression coefficients = -1.098 vs. -0.280, P = 0.018). CONCLUSIONS: An increased CSF level of T-tau was significantly associated with a thinner LCT in both the healthy and AD groups. This result suggests that LCT could serve as a potential non-invasive indicator for increased CSF tau. The clinical meaning of the higher level of CSF T-tau in axonal degeneration of the optic nerve remains to be determined.

Influence of translaminar pressure dynamics on the position of the anterior lamina cribrosa surface.

PURPOSE: To determine how the translaminar pressure difference (TLPD) and gradient (TLPG) influence the position of anterior lamina cribrosa (LC) surface. METHODS: Twenty-six eyes of 26 healthy subjects were subjected to enhanced-depth imaging volume scanning of the optic nerve using spectral-domain optical coherence tomography (SD-OCT). The anterior LC surface depth (LCD) relative to the Bruch's membrane (BM) opening was measured at 11 equidistant planes, and the LC thickness (LCT) was measured at three locations (superior midperipheral, midhorizontal, and inferior midperipheral). Intraocular pressure and lumbar cerebrospinal fluid pressure (CSFP) were measured on the same day as the SD-OCT examination. The TLPD was defined as the difference between IOP and CSFP (i.e., IOP-CSFP), and the TLPG as the TLPD divided by LCT (i.e., TLPD/LCT). RESULTS: Subjects were aged 63.4 ± 8.0 years and comprised 12 males and 14 females. Regression analyses revealed a significant association between a larger mean LCD and male sex (P = 0.002), and between a larger central LCD and male sex (P ≤ 0.012), larger TLPD (P = 0.048), and higher TLPG (P = 0.029). There was no significant association between IOP, CSFP, and LCT, and either the mean LCD (P = 0.438, 0.368, and 0.416, respectively) or central LCD (P = 0.284, 0.085, and 0.144, respectively). CONCLUSIONS: A larger central LCD was associated with larger TLPD and higher TLPG in healthy eyes, which indicates that the translaminar pressure dynamics may play a role in the position of the anterior LC surface relative to BM opening in healthy human eyes.

Morphometry of the trochlear nerve and superior oblique muscle volume in congenital superior oblique palsy.

PURPOSE: To infer the pathogenic mechanism of congenital superior oblique palsy (SOP) by evaluating trochlear nerve diameter (CN4D) and superior oblique muscle (SO) volume in patients with congenital SOP. METHODS: The medical records of 125 patients diagnosed with unilateral congenital SOP and 34 age-matched healthy controls were reviewed retrospectively. Using thin-section high-resolution magnetic resonance imaging, we evaluated the presence of the trochlear nerve, CN4D, SO volume, and their relationship. RESULTS: Of the 125 patients with congenital SOP, 87 showed absence of the trochlear nerve (n = 87, 70%, absent group) and 38 showed bilateral presence of the trochlear nerve (n = 38, 30%, present group). The nonparetic side CN4D was smaller than controls in the absent group (P = 0.001), and larger than controls in the present group (P = 0.001). Trochlear nerve diameter positively correlated with SO volume in controls (P = 0.014, R(2) = 0.174) and in the nonparetic sides of congenital SOP (present group P = 0.023, R(2) = 0.135; absent group, P = 0.008, R(2) = 0.079). The paretic side SO volume did not show a linear correlation between CN4D and SO volume in the present group (P = 0.243). CONCLUSIONS: In congenital SOP patients without a trochlear nerve, the nonparetic side CN4D was also reduced in contrast to those with a trochlear nerve. The relatively weaker relationship of CN4D and nonparetic side SO volume in the absent group than that of the present group suggests different pathogenic mechanisms underlying these two entities of congenital SOP.

Biometric risk factors for corneal neovascularization associated with hydrogel soft contact lens wear in Korean myopic patients.

PURPOSE: To investigate the biometric risk factors for corneal surface complications associated with hydrogel soft contact lens (SCL) fitting in myopic patients in Korea. METHODS: This is a retrospective case-control study. The records of 124 subjects (124 eyes) who wore SCLs on a daily basis were reviewed. Thirty-one patients (31 eyes) who were diagnosed with corneal neovascularization (NV) while wearing SCLs were included in the complication group. Ninety-three age- and sex-matched patients (93 eyes) who wore SCLs, who did not have corneal NV and who visited our clinic for correction of refractive errors were included in the control group. The degree of spherical equivalent, astigmatism and corneal base curve radius (BCR) were compared in both groups. RESULTS: Patients with NV exhibited poorer best corrected visual acuity and more myopia than controls (p = 0.008 and 0.006, respectively). In univariate analysis, highly myopic patients (-9 diopters [D] or higher) were more likely to experience NV (odds ratio [OR], 2.232; 95% confidence interval [CI], 1.602 to 3.105). High astigmatism (≥2 D) increased the risk of complications (OR, 2.717; 95% CI, 1.141 to 6.451). Steep cornea, in which BCR was <7.5 mm, also raised the risk of complications (OR, 4.000; 95% CI, 1.661 to 9.804). Flat cornea was not a risk factor for the development of NV. CONCLUSIONS: High myopia, high astigmatism, and steep cornea seemed to be risk factors in the development of corneal NV in SCL wearers.

The relationship between preoperative and postoperative near stereoacuities and surgical outcomes in intermittent exotropia.

AIMS: To classify patients with intermittent exotropia (IXT) according to the level of near stereopsis, evaluate postoperative stereoacuity and assess the surgical outcomes among groups. METHODS: The records of 137 patients with IXT were reviewed. Patients were divided into three groups based on the degree of stereopsis: good (40-60 arcsec), moderate (80-200 arcsec) and poor (>200 arcsec). These groups were compared with each other with respect to preoperative and postoperative clinical features. RESULTS: Poor stereopsis was found in 19 (13.9%) patients, moderate in 62 (45.2%) and good in 56 (40.9%) patients. There were no statistically significant differences among groups in the mean preoperative and postoperative exodeviations or in the rate of successful surgery. The preoperative and postoperative stereoscopic statuses were similar in each group. Patients with better stereopsis tended to be older when the IXT was first detected and showed better best-corrected visual acuity than those with poorer stereopsis (p=0.027, 0.005, respectively). CONCLUSIONS: Classification of IXT based on the degree of near stereopsis offers a useful tool for the assessment of initial sensory status as well as postoperative prognosis. Also, a lower age at first detection of IXT and a lower best-corrected visual acuity were associated with poor near stereoacuity.

Combined corneal allotransplantation and vitreoretinal surgery using an Eckardt temporary keratoprosthesis: analysis for factors determining corneal allograft survival.

PURPOSE: To evaluate the outcome of corneal allotransplantation in combined penetrating keratoplasty and vitreoretinal surgery using a temporary keratoprosthesis, and to determine the factors affecting corneal allograft survival. METHODS: We reviewed the medical charts of eleven patients who had undergone combined corneal allotransplantation and pars plana vitrectomy using an Eckardt temporary keratoprosthesis, for the treatment of corneal opacification and vitreoretinal disease. The survival rates of the corneal grafts were assessed, and patient demographics, the diagnosis of corneal and retinal disease, the preoperative ocular characteristics, and surgical methods were compared between the group with graft survival and that with graft failure. RESULTS: The causes of corneal opacification were corneal laceration (four eyes), infectious keratitis (four eyes), atopic keratitis (one eye), rejected corneal graft (one eye), and uveitis-related bullous keratopathy (one eye). The preoperative diagnoses included endophthalmitis (six eyes), posterior uveitis (one eye), vitreous opacity or hemorrhage (two eyes), and rhegmatogenous retinal detachment (two eyes). The survival rate of the corneal allografts was 27.3% (3/11 eyes). The mean survival time was 391 days during the mean follow-up period of 687 days. The retinal surgery was successful in 81.8% (9/11 eyes) of cases. The presence of active inflammation in the cornea at the time of surgery was significantly correlated with graft rejection (P=0.004). Other factors, including age, the presence of glaucoma, type of corneal and retinal disease, or type of retinal surgery, such as silicone oil injection and gas tamponade, had no significant correlation with graft rejection. CONCLUSION: Combined corneal allotransplantation and pars plana vitrectomy using a temporary keratoprosthesis allowed for successful surgical intervention in vitreoretinal disease. However, only 27.3% of corneal allografts survived, depending on the presence of active inflammation in the cornea.

Development and validation of a microfluidic chip-based nano-liquid chromatography-triple quadrupole tandem mass spectrometry method for a sensitive and reliable quantification of 7-ethyl-10-hydroxycamptothecin (SN38) in mouse plasma.

There is an increasing need for more sensitive analytical methods in pharmacokinetic studies, for example, for phase 0 clinical trials. A novel HPLC Chip-triple quadrupole mass spectrometer method (HPLC Chip-MS/MS method) for the quantification of 7-ethyl-10-hydroxycamptothecin (SN38) was developed, validated, and employed to the pharmacokinetic analysis of SN38 in ICR mice. Protein precipitation with a ratio of plasma/acetonitrile of 1:10 was chosen as the sample processing method. The nano-electrospray inserted in the microfluidic chip operated in positive mode, and selected reaction monitoring was used for quantification. Our bioanalytical method met all essential validation parameters-selectivity, accuracy, precision, dilution integrity, calibration curve, matrix effect, recovery, and different stability tests (benchtop, freeze-thaw, autosampler stability). The calibration curves (weight 1/x (2)) were linear for the range 50-10,000 pg/mL. Clogging was not observed until the end of the lifetime of the microfluidic chip (350-400 injections), and carryover was practically eliminated through the introduction of a step gradient elution program. After intraperitoneal injection of 0.1 mg/kg irinotecan, SN38 concentration could be measured up to 6 h with accuracy and precision. Thus, we developed a new, very sensitive HPLC Chip-MS/MS method for the determination of plasma SN38 that has been validated in compliance with guidelines from different regulation authorities.

Effect of lateral decubitus position on intraocular pressure in glaucoma patients with asymmetric visual field loss.

PURPOSE: To investigate the effect of the lateral decubitus position (LDP) on intraocular pressure (IOP) in glaucoma patients with asymmetric visual field loss. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Ninety-eight eyes of 49 consecutive bilateral glaucoma patients with asymmetric visual field loss, divided into better eye and worse eye groups for calculation of mean deviation. METHODS: Intraocular pressure was measured using a Goldmann applanation tonometer and rebound tonometer (Icare PRO; Icare Finland Oy, Helsinki, Finland) in each of the following positions: sitting, supine, right LDP, and left LDP. Visual field was examined using the Humphrey Field Analyzer (HFA II; Carl Zeiss Meditec, Dublin, CA). A questionnaire on the preferred lying position during sleep was administered to each of the patients. MAIN OUTCOME MEASURES: The IOPs measured by rebound tonometer for the better and worse eyes in each position were compared using paired t tests. Agreement between the Goldmann applanation tonometry and rebound tonometry results was assessed by a Bland-Altman plot. RESULTS: The IOPs of the better and worse eyes in the sitting position showed no significant difference (P<0.476). The IOP of the worse eye was significantly higher than that of the better eye in the supine position (16.8 ± 3.0 mmHg vs. 15.1 ± 1.8 mmHg; P<0.001). The IOPs of the worse and better eyes in their dependent LDP were 19.1 ± 3.0 mmHg and 17.6 ± 2.3 mmHg, respectively (change in IOP, 1.6 ± 2.4 mmHg; P<0.001). Of the enrolled patients, 75.5% preferred the LDP, and 75.7% of these LDP-preferring patients preferred the worse eye dependent-LDP. The Bland-Altman plot comparing the Goldmann applanation tonometry and rebound tonometry readings showed reasonable agreement between the 2 methods (r(2)<0.001; P = 0.972). CONCLUSIONS: This study showed that IOP-elevation asymmetry in LDP is associated with asymmetric visual field loss in glaucoma patients. The LDP, habitually preferred by glaucoma patients, also may be associated with asymmetric visual field damage.