Lamina Cribrosa Defects and Optic Disc Morphology in Primary Open Angle Glaucoma with High Myopia

Purpose

To investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia.

Methods

A total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure β-peripapillary atrophy (PPA) lengths with and without Bruch''s membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well.

Results

LC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P<0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P<0.001), and larger vertical/horizontal tilt angles (vertical, P<0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P<0.001) and vertical tilt angle (P<0.001) were identified as significant.

Conclusions

The presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.     

Clinical Assessment of Lamina Cribrosa Curvature in Eyes with Primary Open-Angle Glaucoma

Purpose

Quantitative evaluation of lamina cribrosa (LC) posterior bowing in primary open-angle glaucoma (POAG) eyes using swept-source optical coherence tomography.

Methods

Patients with POAG (n = 123 eyes) and healthy individuals of a similar age (n = 92 eyes) were prospectively recruited. Anterior laminar insertion depth (ALID) was defined as the vertical distance between the anterior laminar insertion and a reference plane connecting the Bruch’s membrane openings (BMO). The mean LC depth (mLCD) was approximated by dividing the area enclosed by the anterior LC, the BMO reference plane, and the two vertical lines for ALID measurement by the length between those two vertical lines. The LC curvature index was defined as the difference between the mLCD and the ALID. The factors influencing the LC curvature index were evaluated.

Results

The ALID and mLCD were significantly larger in POAG eyes than in healthy controls (P < 0.05). The LC curvature index was significantly larger in POAG eyes than in healthy controls on both the horizontal (85.8 ± 34.1 vs. 68.2 ± 32.3 μm) and vertical meridians (49.8 ± 38.5 vs. 32.2 ± 31.1 μm, all P < 0.001). Multivariate regression showed significant associations of greater disc area (P < 0.001), vertical C/D ratio (P < 0.001) and mLCD (P < 0.001), smaller rim area (P = 0.001), thinner average RNFLT (P < 0.001), and myopic refraction (P = 0.049) with increased LC curvature index. There was no difference in the LC curvature index between mild (MD > –6 dB) and moderate-to-advanced glaucoma (MD < –6 dB, P = 0.95).

Conclusions

LC posterior bowing was increased in POAG eyes, and was significantly associated with structural optic nerve head (ONH) changes but not with functional glaucoma severity. Quantitative evaluation of LC curvature can facilitate assessment of glaucomatous ONH change.     

Discriminating between Glaucoma and Normal Eyes Using Optical Coherence Tomography and the ‘Random Forests’ Classifier

Purpose

To diagnose glaucoma based on spectral domain optical coherence tomography (SD-OCT) measurements using the ‘Random Forests’ method.

Methods

SD-OCT was conducted in 126 eyes of 126 open angle glaucoma (OAG) patients and 84 eyes of 84 normal subjects. The Random Forests method was then applied to discriminate between glaucoma and normal eyes using 151 OCT parameters including thickness measurements of circumpapillary retinal nerve fiber layer (cpRNFL), the macular RNFL (mRNFL) and the ganglion cell layer-inner plexiform layer combined (GCIPL). The area under the receiver operating characteristic curve (AROC) was calculated using the Random Forests method adopting leave-one-out cross validation. For comparison, AROCs were calculated based on each one of the 151 OCT parameters.

Results

The AROC obtained with the Random Forests method was 98.5% [95% Confidence interval (CI): 97.1–99.9%], which was significantly larger than the AROCs derived from any single OCT parameter (maxima were: 92.8 [CI: 89.4–96.2] %, 94.3 [CI: 91.1–97.6] % and 91.8 [CI: 88.2–95.4] % for cpRNFL-, mRNFL- and GCIPL-related parameters, respectively; P<0.05, DeLong’s method with Holm’s correction for multiple comparisons). The partial AROC above specificity of 80%, for the Random Forests method was equal to 18.5 [CI: 16.8–19.6] %, which was also significantly larger than the AROCs of any single OCT parameter (P<0.05, Bootstrap method with Holm’s correction for multiple comparisons).

Conclusions

The Random Forests method, analyzing multiple SD-OCT parameters concurrently, significantly improves the diagnosis of glaucoma compared with using any single SD-OCT measurement.     

Reproducibility of In-Vivo OCT Measured Three-Dimensional Human Lamina Cribrosa Microarchitecture

Purpose

To determine the reproducibility of automated segmentation of the three-dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using optical coherence tomography (OCT).

Methods

Thirty-nine eyes (8 healthy, 19 glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using swept-source (SS−) OCT in a 3.5×3.5×3.64 mm (400×400×896 pixels) volume centered on the optic nerve head, with the focus readjusted after each scan. The LC was automatically segmented and analyzed for microarchitectural parameters, including pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore area, beam thickness, beam thickness SD, and beam thickness to pore diameter ratio. Reproducibility of the parameters was assessed by computing the imprecision of the parameters between the scans.

Results

The automated segmentation demonstrated excellent reproducibility. All LC microarchitecture parameters had an imprecision of less or equal to 4.2%. There was little variability in imprecision with respect to diagnostic category, although the method tends to show higher imprecision amongst healthy subjects.

Conclusion

The proposed automated segmentation of the LC demonstrated high reproducibility for 3D LC parameters. This segmentation analysis tool will be useful for in-vivo studies of the LC.     

IOL Tilt and Decentration Estimation from 3 Dimensional Reconstruction of OCT Image

Purpose

To evaluate intraocular lens (IOL) tilt and decentration by anterior segment optical coherence tomography (AS-OCT) using 3-dimensional (3D) reconstruction method.

Design

Prospective observational case series.

Participants

Thirty-nine patients (39 eyes) were included.

Methods

The IOL positions of all eyes were examined by AS-OCT. Images were obtained in 4 axes (0–180 degrees, 45–225 degrees, 90–270 degrees, and 135–315 degrees) using the quadrant-scan model. The cross-sectional images were analyzed with MATLAB software.

Main Outcome Measures

The angle (θ) between the reference pupillary plane and the IOL plane, the distances between the center points of the pupil circle and the IOL on the x-axis (dx) and y-axis (dy) and the spatial distance (ds) were calculated after 3D-reconstruction.

Results

The mean angle (θ) between the pupillary plane and the IOL plane was 2.94±0.99 degrees. The mean IOL decentration of dx and dy was 0.32±0.26 mm and 0.40±0.27 mm, respectively. The ds of the IOL decentration was 0.56±0.31 mm. There was no significant correlation between the ocular residual astigmatism (ORA) and the tilted angle or the decentration distance. There was a significant correlation between the ORA and total astigmatism (r = 0.742, P<0.001). There was no significant correlation between the postoperative best corrected visual acuity (BCVA) and the ORA (r = 0.156; P = 0.344), total astigmatism (r = 0.012; P = 0.942), tilted angle (θ; r = 0.172; P = 0.295) or decentration distance (dx: r = 0.191, P = 0.244; dy: r = 0.253, P = 0.121; ds: r = 0.298, P = 0.065).

Conclusions

AS-OCT can be used as an alternative for the analysis of IOL tilt and decentration using 3D-reconstruction.     

Defects of the Lamina Cribrosa in High Myopia and Glaucoma

Purpose

We evaluated the prevalence and characteristics of the defects of the lamina cribrosa (LC) in high myopia and glaucoma, and compared them with control eyes using swept-source optical coherence tomography (SS-OCT).

Methods

One hundred fifty-nine eyes of 108 participants were divided into four subgroups; high myopia with glaucoma (MG, 67 eyes of 46 subjects), glaucoma without high myopia (G, 22 eyes of 13 subjects), high myopia without glaucoma (M, 35 eyes of 29 subjects), and a control group with neither glaucoma nor high myopia (C, 35 eyes of 20 subjects). The LC defects were identified and located using a standardized protocol in serial horizontal OCT scans. The prevalence rates of the defects were compared among the groups. Demographic and ocular factors were compared between eyes with and without defects.

Results

LC defects were observed in one eye (0.03%) in the C group, 8 eyes (22.9%) in the M group, 11 eyes (50%) in the G group, and 28 eyes (41.8%) in the MG group. The prevalence rates of the defects differed significantly among the groups (P = 0.0009). Most eyes with defects in the G and MG groups (79.5%) had damage in the corresponding visual hemifields. Other factors such as visual acuity, intraocular pressure, axial length, refractive error, disc ovality, or parapapillary atrophy area did not differ significantly between eyes with and without LC defects.

Conclusions

High myopia and glaucoma significantly increased the risk of LC damage. The LC damage in non-glaucomatous highly myopic eyes may at least partly explain the increased risk of developing glaucoma in myopic eyes.     

Distribution of Central Corneal Thickness and its Association with Ocular Parameters in a Large Central European Cohort: The Gutenberg Health Study

Main objective

To evaluate the distribution of central corneal thickness (CCT) in a large German cohort and to analyse its relationship with intraocular pressure and further ocular factors.

Design

Population-based, prospective, cohort study.

Methods

The Gutenberg Health Study (GHS) cohort included 4,698 eligible enrollees of 5,000 subjects (age range 35–74 years) who participated in the survey from 2007 to 2008. All participants underwent an ophthalmological examination including slitlamp biomicroscopy, intraocular pressure measurement, central corneal thickness measurement, fundus examination, and were given a questionnaire regarding glaucoma history. Furthermore, all subjects underwent fundus photography and visual field testing using frequency doubling perimetry.

Results

Mean CCT was 557.3±34.3 µm (male) and 551.6±35.2 µm in female subjects (Mean CCT from right and left eyes). Younger male participants (35–44 years) presented slightly thicker CCT than those older. We noted a significant CCT difference of 4 µm between right and left eyes, but a high correlation between eyes (Wilcoxon test for related samples: p<0.0001). Univariable linear regression stratified by gender showed that IOP was correlated with CCT (p<0.0001). A 10 µm increase in CCT led to an increase in IOP between 0.35–0.38 mm Hg, depending on the eye and gender. Multivariable linear regression analysis revealed correlations between gender, spherical equivalent (right eyes), and CCT (p<.0001 and p = 0.03, respectively).

Conclusions

We observed positive correlations between CCT and IOP and gender. CCT was not correlated with age, contact lens wear, positive family history for glaucoma, lens status, or iris colour.     

Long-Term Outcomes and Complications of Trabeculectomy for Secondary Glaucoma in Patients with Familial Amyloidotic Polyneuropathy

Objective

Secondary glaucoma is a serious complication in patients with transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP). We assessed the long-term outcomes and complications of trabeculectomy with mitomycin C (MMC) for secondary glaucoma associated with FAP.

Methods

Medical case records of Kumamoto University Hospital were retrospectively reviewed. Twenty-one eyes of 13 patients (10 with FAP ATTR Val30Met; 3 with FAP ATTR Tyr114Cys) underwent trabeculectomy with MMC and follow-up of at least 2 years. The primary outcome measure was Kaplan-Meier survival, with failure of this treatment being defined as an intraocular pressure (IOP) of ≤5 mm Hg or ≥22 mm Hg on two consecutive visits or as additional operations needed to reduce IOP. Secondary outcome measures included complications, bleb characteristics, and additional postoperative interventions required.

Results

The mean postoperative follow-up period was 5.7 years (range, 2.2–12.7 years). Kaplan-Meier analysis indicated probabilities of success of 0.76, 0.67, and 0.53 at 1, 2, and 3 years after operation, respectively. Significant complications included ocular decompression retinopathy in 7 eyes (33%) and bleb encapsulation in 10 eyes (48%). Twelve eyes (57%) needed additional surgery, such as bleb revision or trabeculectomy with MMC, to reduce IOP.

Conclusions

Trabeculectomy with MMC may not be optimal for patients with FAP-related glaucoma and may have several significant complications.     

A Laser-Induced Mouse Model with Long-Term Intraocular Pressure Elevation

Purpose

To develop and characterize a mouse model with intraocular pressure (IOP) elevation after laser photocoagulation on the trabecular meshwork (TM), which may serve as a model to investigate the potential of stem cell-based therapies for glaucoma.

Methods

IOP was measured in 281 adult C57BL/6 mice to determine normal IOP range. IOP elevation was induced unilaterally in 50 adult mice, by targeting the TM through the limbus with a 532-nm diode laser. IOP was measured up to 24 weeks post-treatment. The optic nerve damage was detected by electroretinography and assessed by semiautomatic counting of optic nerve axons. Effects of laser treatment on the TM were evaluated by histology, immunofluorescence staining, optical coherence tomography (OCT) and transmission electron microscopy (TEM).

Results

The average IOP of C57BL/6 mice was 14.5±2.6 mmHg (Mean ±SD). After laser treatment, IOP averaged above 20 mmHg throughout the follow-up period of 24 weeks. At 24 weeks, 57% of treated eyes had elevated IOP with the mean IOP of 22.5±2.5 mmHg (Mean ±SED). The difference of average axon count (59.0%) between laser treated and untreated eyes was statistically significant. Photopic negative response (PhNR) by electroretinography was significantly decreased. CD45+ inflammatory cells invaded the TM within 1 week. The expression of SPARC was increased in the TM from 1 to 12 weeks. Histology showed the anterior chamber angle open after laser treatment. OCT indicated that most of the eyes with laser treatment had no synechia in the anterior chamber angles. TEM demonstrated disorganized and compacted extracellular matrix in the TM.

Conclusions

An experimental murine ocular hypertension model with an open angle and optic nerve axon loss was produced with laser photocoagulation, which could be used to investigate stem cell-based therapies for restoration of the outflow pathway integrity for ocular hypertension or glaucoma.     

Transorbital Sonographic Evaluation of Normal Optic Nerve Sheath Diameter in Healthy Volunteers in Bangladesh

Introduction

Measurement of optic nerve sheath diameter (ONSD) by ultrasound is increasingly used as a marker to detect raised intracranial pressure (ICP). ONSD varies with age and there is no clear consensus between studies for an upper limit of normal. Knowledge of normal ONSD in a healthy population is essential to interpret this measurement.

Methods

In a prospective observational study, ONSD was measured using a 15 MHz ultrasound probe in healthy volunteers in Chittagong, Bangladesh. The aims were to determine the normal range of ONSD in healthy Bangladeshi adults and children, compare measurements in males and females, horizontal and vertical beam orientations and left and right eyes in the same individual and to determine whether ONSD varies with head circumference independent of age.

Results

136 subjects were enrolled, 12.5% of whom were age 16 or under. Median ONSD was 4.41 mm with 95% of subjects in the range 4.25–4.75 mm. ONSD was bimodally distributed. There was no relationship between ONSD and age (≥4 years), gender, head circumference, and no difference in left vs right eye or horizontal vs vertical beam.

Conclusions

Ultrasonographic ONSD in Bangladeshi healthy volunteers has a narrow bimodal distribution independent of age (≥4 years), gender and head circumference. ONSD >4.75 mm in this population should be considered abnormal.     

Biometry of Anterior Segment of Human Eye on Both Horizontal and Vertical Meridians during Accommodation Imaged with Extended Scan Depth Optical Coherence Tomography

Purpose

To determine the biometry of anterior segment dimensions of the human eye on both horizontal and vertical meridians with extended scan depth optical coherence tomography (OCT) during accommodation.

Methods

Twenty pre-presbyopic volunteers, aged between 24 and 30, were recruited. The ocular anterior segment of each subject was imaged using an extended scan depth OCT under non- and 3.0 diopters (D) of accommodative demands on both horizontal and vertical meridians. All the images were analyzed to yield the following parameters: pupil diameter (PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive measurements were performed to assess the repeatability and reproducibility of this OCT. They were evaluated by calculating the within-subject standard deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and the coefficient of repeatability/reproducibility (CoR).

Results

There were no significant differences between two consecutive measurements on either horizontal or vertical meridians under both two different accommodative statuses (P>0.05). The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550) on the horizontal meridian under the non-accommodative status. In addition, the CoR for most of the parameters were excellent (0.004% to 4.89%). In all the parameters, only PD and PSC were found different between the horizontal and vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and PSC under accommodative status were significantly smaller than those under the non-accommodative status, except that the PSC at the vertical meridian did not change. In addition, LT was significantly increased when accommodation.

Conclusion

The extended scan depth OCT successfully measured the dimensions of the anterior eye during accommodation with good repeatability and reproducibility on both horizontal and vertical meridians. The asymmetry of lens posterior surface and oval-shaped pupil were found during accommodation.     

Vertical and Horizontal Corneal Epithelial Thickness Profile Using Ultra-High Resolution and Long Scan Depth Optical Coherence Tomography

Purpose

To determine the vertical and horizontal thickness profiles of the corneal epithelium in vivo using ultra-long scan depth and ultra-high resolution spectral domain optical coherence tomography (SD-OCT).

Methods

A SD-OCT was developed with an axial resolution of ∼3.3 µm in tissue and an extended scan depth. Forty-two eyes of 21 subjects were imaged twice. The entire horizontal and vertical corneal epithelial thickness profiles were evaluated. The coefficient of repeatability (CoR) and intraclass correlation (ICC) of the tests and interobserver variability were analyzed.

Results

The full width of the horizontal epithelium was detected, whereas part of the superior epithelium was not shown for the covered super eyelid. The mean central epithelial corneal thickness was 52.0±3.2 µm for the first measurement and 52.3±3.4 µm for the second measurement (P>.05). In the central zone (0–3.0 mm), the paracentral zones (3.0–6.0 mm) and the peripheral zones (6.0–10.0 mm), the mean epithelial thickness ranged from 51 to 53 µm, 52 to 57 µm, and 58 to 72 µm, respectively. There was no difference between the two tests at both meridians and in the right and left eyes (P>.05). The ICCs of the two tests ranged from 0.70 to 0.97 and the CoRs ranged from 2.5 µm to 7.8 µm from the center to the periphery, corresponding to 5.6% to 10.6% (CoR%). The ICCs of the two observers ranged from 0.72 to 0.93 and the CoRs ranged from 4.5 µm to 10.4 µm from the center to the periphery, corresponding to 8.7% to 15.2% (CoR%).

Conclusions

This study demonstrated good repeatability of ultra-high resolution and long scan depth SD-OCT to evaluate the entire thickness profiles of the corneal epithelium. The epithelial thickness increases from the center toward the limbus.     

Glaucoma-Induced Optic Disc Morphometric Changes and Glaucoma Diagnostic Ability of Heidelberg Retina Tomograph II in Highly Myopic Eyes

Purpose

This study was performed to first investigate the morphological differences in the optic nerve head between highly myopic non-glaucomatous controls and highly myopic glaucomatous eyes in comparison with the differences between emmetropic non-glaucomatous controls and emmetropic glaucomatous eyes using confocal scanning laser ophthalmoscopy. Further, the ability of the apparatus in glaucoma diagnosis in highly myopic eyes was compared with that in emmetropic eyes.

Methods

Healthy subjects and age-matched patients with early-stage open-angle glaucoma were divided into two groups: emmetropic eyes (−1.0 to +1.0 diopters) and highly myopic eyes (−12.0 to −5.0 diopters).The participants were comprised of 65 emmetropic normal eyes, 59 emmetropic glaucomatous eyes, 62 highly myopic normal eyes, and 68 highly myopic glaucomatous eyes and eyes with pathologic myopia were carefully excluded. Confocal scanning laser tomographic parameters were compared among all subjects after adjustment for age and disc area. The ROC curves and sensitivity and specificity for glaucoma detection using several clinical methods were then compared between the emmetropic and highly myopic eyes.

Results

Rim area, cup/disc area ratio, mean cup depth, and cup shape measure of glaucoma eyes are significantly different from those of normal eyes in both highly myopic eyes and emmetropic eyes. Methodological overestimation of retinal nerve fiber layer cross sectional area due to optic disc tilting was suggested in the highly myopic eyes. The diagnostic performance of glaucoma using several discriminant methods significantly deteriorated in the highly myopic eyes.

Conclusions

In the highly myopic glaucomatous eyes, confocal scanning laser tomographic parameters were significantly different from that of non-glaucomatous highly myopic eyes but diagnostic performance of glaucoma was deteriorated than that in emmetropic eyes. These findings demonstrate the utility and limitations of the apparatus in diagnosing glaucoma in highly myopic patients.     

Assessment of Choroidal Thickness in Healthy and Glaucomatous Eyes Using Swept Source Optical Coherence Tomography

Purpose

To evaluate choroidal thickness (CT) in healthy and glaucomatous eyes using Swept Source Optical Coherence Tomography (SS-OCT).

Methods

A cross-sectional observational study of 216 eyes of 140 subjects with glaucoma and 106 eyes of 67 healthy subjects enrolled in the Diagnostic Innovations in Glaucoma Study. CT was assessed from wide-field (12×9 mm) SS-OCT scans. The association between CT and potential confounding variables including age, gender, axial length, intraocular pressure, central corneal thickness and ocular perfusion pressure was examined using univariable and multivariable regression analyses.

Results

Overall CT was thinner in glaucomatous eyes with a mean (± standard deviation) of 157.7±48.5 µm in glaucoma compared to 179.9±36.1 µm in healthy eyes (P<0.001). The choroid was thinner in both the peripapillary and macular regions in glaucoma compared to controls. Mean peripapillary CT was 154.1±44.1 µm and 134.0±56.9 µm (P<0.001) and macular CT 199.3±46.1 µm and 176.2±57.5 µm (P<0.001) for healthy and glaucomatous eyes respectively. However, older age (P<0.001) and longer axial length (P<0.001) were also associated with thinner choroid and when differences in age and axial length between glaucomatous and healthy subjects were accounted for, glaucoma was not significantly associated with CT. There was also no association between glaucoma severity and CT.

Conclusions

Glaucoma was not associated with CT measured using SS-OCT; however, older age and longer axial length were associated with thinner choroid so should be considered when interpreting CT measurements.     

A Simple Sign for Recognizing Off–Axis OCT Measurement Beam Placement in the Context of Multicentre Studies

Purpose

Optical coherence tomography (OCT) allows quantification of the thickness of the retinal nerve fibre layer (RNFL) thickness, a potential biomarker for neurodegeneration. The estimated annual RNFL loss in multiple sclerosis amounts to 2 μm using time domain OCT. The recognition of measurement artifacts exceeding this limit is relevant for the successful use of OCT as a secondary outcome measure in clinical trials.

Methods

Prospective study design. An exploratory pilot study (ring and volume scans) followed by a cohort study (1,980 OCT ring scans). The OCT measurement beam was placed off–axis to the left, right, top and bottom of the subjects pupil and RNFL thickness of these scans were compared to the centrally placed reference scans.

Results

Off–axis placement of the OCT measurement beam resulted in significant artifacts in RNFL thickness measurements (95%CI 9μm, maximal size of error 42μm). Off–axis placement gave characteristic patterns of the OCT live images which are not necessarily saved for review. Off–axis placement also causes regional inhomogeneity of reflectivity in the outer nuclear (ONL) and outer plexiform layers (OPL) which remains visible on scans saved for review.

Conclusion

Off–axis beam placement introduces measurement artifacts at a magnitude which may mask recognition of RNFL loss due to neurodegeneration in multiple sclerosis. The resulting pattern in the OCT live image can only be recognised by the technician capturing the scans. Once the averaged scans have been aligned this pattern is lost. Retrospective identification of this artifact is however possible by presence of regional inhomogeneity of ONL/OPL reflectivity. This simple and robust sign may be considered for quality control criteria in the setting of multicentre OCT studies. The practical advice of this study is to keep the OCT image in the acquisition window horizontally aligned whenever possible.     

Vitreous Hyper-Reflective Dots in Optical Coherence Tomography and Cystoid Macular Edema after Uneventful Phacoemulsification Surgery

Purpose

To report the observation of hyper-reflective dots in the vitreous cavity using spectral domain optical coherence tomography (SD-OCT) after uneventful phacoemulsification cataract surgery and to investigate their association with cystoid macular edema (CME).

Materials and Methods

Medical records of consecutive Asian patients who had no preoperative retinopathy and underwent uneventful phacoemulsification cataract surgery from March 2012 through February 2013 were reviewed. SD-OCTs were performed before, 1 week, and 1 month after surgery. The number of vitreous hyper-reflective dots (VHDs) was counted in 5 OCT images of high-definition 5-line raster scans. The development of CME was assessed using postoperative 1-month OCT.

Results

In 74 eyes of 74 patients, all of three SD-OCTs with a signal to noise ratio of 0.6 or more were available and were analyzed in this study. In preoperative OCT, the VHD was observed in 2 (2.7%) of 74 eyes; one eye had 1 VHD and the other eye had 2 VHDs. In 72 eyes with no preoperative VHD, VHDs were observed in 40 (55.6%) eyes at 1 week after the surgery. In the multivariate analysis, the number of VHDs measured at 1 week after the surgery was significantly associated with CME development at 1 month after the surgery (odds ratio = 1.93, 95% confidence interval = 1.15 to 3.24, P = 0.012).

Conclusions

VHDs were frequently observed in OCT after uneventful phacoemulsification cataract surgery. VHDs observed at 1 week after the surgery may be a risk factor for the development of pseudophakic CME. Further studies are needed to identify the source of the VHDs.     

A Randomized,Placebo Controlled Pilot Trial of Botulinum Toxin for Paratonic Rigidity in People with Advanced Cognitive Impairment

Objective

Evaluate safety and efficacy of Incobotulinumtoxin A in elderly patients with dementia and paratonia.

Setting

University-affiliated hospital, spasticity management Clinic.

Participants

Ten subjects were enrolled. Inclusion criteria: 1) severe cognitive impairment 2) diagnosis of Alzheimer’s disease, vascular dementia, or frontotemporal dementia, and 3) score >3 on the paratonic assessment instrument, with posture in an arm(s) interfering with provision of care. Exclusion criteria: 1) alternate etiologies for increased tone and 2) injection with botulinum toxin within the 6 months preceding the study.

Design

Single center, randomized, double blind, placebo-controlled, crossover trial with two treatment cycles of 16 weeks. Assessments occurred at 2, 6, 12 and16 weeks following injections. Subjects received up to 300 U of Incobotulinumtoxin A in arm(s).

Primary and Secondary Outcome Measures

Primary outcome measure was the modified caregiver burden scale (mCBS); exploratory secondary outcome measures were also performed. Analysis of variance and mixed modeling techniques were used to evaluate treatment effects.

Results

Incobotulinumtoxin A treatment produced significant improvement in mCBS total score −1.11 (–2.04 to −0.18) (Treatment effect and 95% CI), dressing sub-score −0.36 (–0.59 to 0.12), and cleaning under the left and right armpits sub-score −0.5 (–0.96 to −0.04), −0.41 (–0.79 to −0.04) respectively. PROM in the left and right elbow increased by 27.67 degrees (13.32–42.02) and 22.07 degrees (9.76–34.39) respectively. PROM in the left and right shoulder increased by 11.92 degrees (5.46–18.38) and 8.58 degrees (3.73–13.43) respectively. No significant treatment effect was found for GAS, VAS and PAINAD scales or change in time to perform care. No adverse drug reactions occurred.

Conclusions

Administration of Incobotulinumtoxin A in elderly people with advanced dementia and paratonia may be an efficacious and safe treatment to increase range of motion and reduce functional burden. Further studies are needed to confirm results.

Trial Registration

ClinicalTrials.Gov {"type":"clinical-trial","attrs":{"text":"NCT02212119","term_id":"NCT02212119"}}NCT02212119     

Analysis of Fundus Shape in Highly Myopic Eyes by Using Curvature Maps Constructed from Optical Coherence Tomography

Purpose

To evaluate fundus shape in highly myopic eyes using color maps created through optical coherence tomography (OCT) image analysis.

Methods

We retrospectively evaluated 182 highly myopic eyes from 113 patients. After obtaining 12 lines of 9-mm radial OCT scans with the fovea at the center, the Bruch’s membrane line was plotted and its curvature was measured at 1-µm intervals in each image, which was reflected as a color topography map. For the quantitative analysis of the eye shape, mean absolute curvature and variance of curvature were calculated.

Results

The color maps allowed staphyloma visualization as a ring of green color at the edge and as that of orange-red color at the bottom. Analyses of mean and variance of curvature revealed that eyes with myopic choroidal neovascularization tended to have relatively flat posterior poles with smooth surfaces, while eyes with chorioretinal atrophy exhibited a steep, curved shape with an undulated surface (P<0.001). Furthermore, eyes with staphylomas and those without clearly differed in terms of mean curvature and the variance of curvature: 98.4% of eyes with staphylomas had mean curvature ≥7.8×10⁻⁵ [1/µm] and variance of curvature ≥0.26×10⁻⁸ [1/µm].

Conclusions

We established a novel method to analyze posterior pole shape by using OCT images to construct curvature maps. Our quantitative analysis revealed that fundus shape is associated with myopic complications. These values were also effective in distinguishing eyes with staphylomas from those without. This tool for the quantitative evaluation of eye shape should facilitate future research of myopic complications.     

Estimated Rates of Retinal Ganglion Cell Loss in Glaucomatous Eyes with and without Optic Disc Hemorrhages

Purpose

To evaluate whether optic disc hemorrhages are associated with faster rates of estimated retinal ganglion cell (RGC) loss in glaucoma.

Methods

A longitudinal observational cohort study of 222 eyes of 122 patients with glaucoma recruited from the Diagnostic Innovations Glaucoma Study (DIGS) followed for an average of 3.74±0.85 years. All subjects had optical coherence tomography and standard automated perimetry during follow up. Optic disc hemorrhages were detected by masked evaluation of stereophotographs. Rates of change in estimated numbers of RGCs were determined using a previously described method. A random coefficients model was used to investigate the relationship between disc hemorrhages and rates of change in estimated RGC counts over time.

Results

19 eyes of 18 subjects had at least one disc hemorrhage during follow up. At baseline, average estimated RGC counts in eyes with and without disc hemorrhages were 677,994 cells and 682,021 cells, respectively (P = 0.929). Eyes with optic disc hemorrhages during follow-up had significantly faster rates of estimated RGC loss than eyes without disc hemorrhages (22,233 cells/year versus 10,704 cells/year, P = 0.020). The effect of disc hemorrhages on the rates of estimated RGC loss remained significant after adjusting for confounding variables.

Conclusion

Eyes with disc hemorrhages showed faster rates of RGC loss compared to eyes without disc hemorrhages. These results provide further evidence that disc hemorrhages should be considered as an indicator of increased risk for faster neural loss in glaucoma.     

One-Step Transepithelial Topography-Guided Ablation in the Treatment of Myopic Astigmatism

Purpose

To evaluate one-step topography-guided transepithelial ablation in the treatment of low to moderate myopic astigmatism using a 1KHz excimer laser.

Methods

Retrospective study of 117 consecutive eyes available for evaluation 12 months after surgery. Pre- and post-operative visual and refractive data as well as post-operative pain and haze were analyzed. A novel technique integrating custom refractive- and epithelial- ablation in a single uninterrupted procedure was used.

Results

The mean pre-operative spherical equivalent (SE) and the mean cylinder were: –3.22 diopters (D) ±1.54 (SD) (range –0.63 to –7.25 D) and –0.77 D ±0.65 (range 0 to –4.50 D), respectively. At 12 months after surgery: no eyes lost ≥2 lines of corrected distant visual acuity (CDVA). Safety and efficacy indexes were 1.27 and 1.09, respectively. Uncorrected distant visual acuity (UDVA) was ≥20/20 in 96.6% of the eyes. Manifest refraction spherical equivalent was within ±0.5 D of the desired refraction in 93.2% of the eyes. Average root mean square (RMS) wavefront error measured at central 6 mm, increased from 0.38 pre-operatively to 0.47 µm post-operatively. Refractive stability was achieved and sustained 1 month after surgery. No visually significant haze was registered during the observation period. Post-operative pain was reported in 4.5% of patients.

Conclusions

One-step transepithelial topography-guided treatment for low to moderate myopia and astigmatism performed with a 1 KHz laser, provided safe, effective, predictable and stable results with low pain and no visually significant haze.