Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.

Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights into the complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during aging, despite normal intraocular pressure (IOP), resembling a phenotype of normal-tension glaucoma. These detrimental effects were potentially mediated by accelerated RGC senescence through Caveolin-1 upregulation and by the induction of mitochondrial dysfunction. In mouse models of high-tension glaucoma, Sirt6 level was decreased after IOP elevation. Genetic overexpression of Sirt6 globally or specifically in RGCs significantly attenuated high tension-induced degeneration of RGCs and their axons, whereas partial or RGC-specific Sirt6 deletion accelerated RGC loss. Importantly, therapeutically targeting Sirt6 with pharmacological activator or AAV2-mediated gene delivery ameliorated high IOP-induced RGC degeneration. Together, our studies reveal a critical role of Sirt6 in preventing RGC and optic nerve degeneration during aging and glaucoma, setting the stage for further exploration of Sirt6 activation as a potential therapy for glaucoma.

Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Utilization of Portable Radios to Improve Ophthalmology Clinic Efficiency in an Academic Setting.

Improvement in clinic efficiency in the ambulatory setting is often looked at as an area for development of lean management strategies to deliver a higher quality of healthcare while reducing errors, costs, and delays. To examine the benefits of improving team communication and its impact on clinic flow and efficiency, we describe a time-motion study performed in an academic outpatient Ophthalmology clinic and its objective and subjective results. Compared to clinic encounters without the use of the portable radios, objective data demonstrated an overall significant decreases in mean workup time (15.18 vs. 13.10), room wait (13.10 vs. 10.47), and decreased the total time needed with an MD per encounter (9.45 vs. 6.63). Subjectively, significant improvements were seen in careprovider scores for patient flow (60.78 vs. 84.29), getting assistance (61.89 vs. 88.57), moving patient charts (54.44 vs. 85.71), teamwork (69.56 vs. 91.0), communications (62.33 vs. 90.43), providing quality patient care (76.22 vs. 89.57), and receiving input on the ability to see walk-in patients (80.11 vs. 90.43). For academic purposes, an improvement in engagement in patient care and learning opportunities was noted by the clinic resident-in-training during the pilot study. Portable radios in our pilot study were preferred over the previous method of communication and demonstrates significant improvements in certain areas of clinical efficiency, subjective perception of teamwork and communications, and academic learning.

Ocular outcomes evaluation in a 14-day head-down bed rest study.

INTRODUCTION: We evaluated ocular outcomes in a 14-d head-down tilt (HDT) bed rest (BR) study designed to simulate the effects of microgravity on the human body. METHODS: Healthy subjects were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented (e.g., strict sleep-wake cycle, standardized diet, 24-hour-a-day BR, continuous video monitoring). Subjects maintained a 6° HDT position for 14 consecutive days. Weekly ophthalmological examinations were performed in the sitting (pre/post-BR) and HDT (in-bed phase) positions. Equivalency tests with optimal-alpha techniques evaluated pre/post-BR differences in best-corrected visual acuity (BCVA), spherical equivalent, intraocular pressure (IOP), Spectral-domain OCT retinal nerve fiber layer thickness (RNFLT), optic disc and macular parameters. RESULTS: 16 subjects (12 men and 4 women) were enrolled. Nearly all ocular outcomes were within our predefined clinically relevant thresholds following HDTBR, except near BCVA (pre/post-BR mean difference: -0.06 logMAR), spherical equivalent (-0.30 D), Tonopen XL IOP (+3.03 mmHg) and Spectralis OCT average (+1.14 µm), temporal-inferior (+1.58 µm) and nasal-inferior RNFLT (+3.48 µm). Modified Amsler grid, red dot test, confrontational visual field, and color vision were within normal limits throughout. No changes were detected on stereoscopic color fundus photography. DISCUSSION: A few functional and structural changes were detected after 14-d HDTBR, notably an improved BCVA possibly due to learning effect and RNFL thickening without signs of optic disc edema. In general, 6° HDTBR determined a small nonprogressive IOP elevation, which returned to baseline levels post-BR. Further studies with different BR duration and/or tilt angle are warranted to investigate microgravity-induced ophthalmological changes.

Ultrasound Biomicroscopy as a Novel, Potential Modality to Evaluate Anterior Segment Ophthalmic Structures during Spaceflight: An Analysis of Current Technology.

Ocular health is currently a major concern for astronauts on current and future long-duration spaceflight missions. Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of ophthalmic and neurologic findings that is one potential physiologic barrier to interplanetary spaceflight. Since its initial report in 2011, our understanding of SANS has advanced considerably, with a primary focus on posterior ocular imaging including fundus photography and optical coherence tomography. However, there may be changes to the anterior segment that have not been identified. Additional concerns to ocular health in space include corneal damage and radiation-induced cataract formation. Given these concerns, precision anterior segment imaging of the eye would be a valuable addition to future long-duration spaceflights. The purpose of this paper is to review ultrasound biomicroscopy (UBM) and its potential as a noninvasive, efficient imaging modality for spaceflight. The analysis of UBM for spaceflight is not well defined in the literature, and such technology may help to provide further insights into the overall anatomical changes in the eye in microgravity.

Intraocular pressure and steep Trendelenburg during minimally invasive gynecologic surgery: is there a risk?

STUDY OBJECTIVE: Steep Trendelenburg position is frequently used during gynecologic minimally invasive surgery (MIS). However, little attention has been given to the potential impact of this nonphysiologic positioning on patients, specifically intraocular pressure (IOP). The purpose of our study was to evaluate IOP changes during laparoscopic or robotic hysterectomy conducted in the steep Trendelenburg position. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: John Sealy Hospital at the University of Texas Medical Branch, Galveston, TX. PATIENTS: Female patients with no history of ocular pathology who underwent elective robotic or laparoscopic hysterectomy. INTERVENTIONS: The anesthesia protocol was standardized for all study patients. IOP and mean arterial pressure (MAP) were obtained before anesthesia, after general anesthesia and intubation were achieved, after 1 hour of steep Trendelenburg positioning, after 2 hours of steep Trendelenburg positioning, and after the patient was returned to the supine position. Ocular perfusion pressure (OPP) was calculated using the following equation: OPP = MAP - IOP. MAIN RESULTS: A total of 10 patients were included in this prospective study. A significant increase in IOP from baseline was observed after 1 hour and 2 hours of steep Trendelenburg positioning (p = .005 and .002, respectively). There was a statistically significant trend of increasing the IOP from baseline to the second hour of steep Trendelenburg positioning (p < .001). The IOP remained significantly elevated once the patient was returned to the supine position when compared with the baseline IOP (p = .006). OPP significantly decreased from baseline after 2 hours of steep Trendelenburg positioning (p = .03). CONCLUSIONS: IOP increases significantly when patients are placed in the steep Trendelenburg position. Although further studies are needed to better characterize this process, given the aging population of our MIS patients in whom risk for glaucoma is significant, preoperative ocular health assessment should be considered in certain cases.

Effects of 30-day head-down bed rest on ocular structures and visual function in a healthy subject.

INTRODUCTION: We report ocular changes occurring in a healthy human subject enrolled in a bed rest (BR) study designed to replicate the effects of a low-gravity environment. CASE REPORT: A 25-yr-old Caucasian man spent 30 consecutive days in a 6 degrees head-down tilt (HDT) position at the NASA Flight Analogs Research Unit. Comprehensive ophthalmologic exams, optic disc stereo-photography, standard automated perimetry (SAP), and optic disc Spectralis OCT scans were performed at baseline, immediately post-BR (BR+0), and 6 mo post-BR. MAIN OUTCOME MEASURES: changes in best-corrected visual acuity, intraocular pressure (IOP), cycloplegic refraction, SAP, and Spectralis OCT measures. At BR+0 KIOP was 11 and 10 mmHg in the right (OD) and left eye (OS), respectively (a bilateral 4-mmHg decrease compared to baseline); SAP documented a possible bilateral symmetrical inferior scotoma; Spectralis OCT showed an average 19.4 microm (+5.2%) increase in peripapillary retinal thickness, and an average 0.03 mm3 (+5.0%) increase in peripapillary retinal volume bilaterally. However, there were no clinically detectable signs of optic disc edema. At 6 mo post-BR, IOP was 13 and 14 mmHg in OD and OS, respectively, and the scotoma had resolved. Spectralis OCT measurements matched the ones recorded at baseline. DISCUSSION: In this subject, a reduction in IOP associated with subtle structural and functional changes compared to baseline were documented after prolonged head-down BR. These changes may be related to cephalad fluid shifts in response to tilt. Further studies should clarify whether decreased translaminar pressure (i.e., the difference between IOP and intracranial pressure) may be responsible for these findings.

FK506 Treatment Prevents Retinal Nerve Fiber Layer Thinning in Organ-Transplanted Glaucoma Patients: A Retrospective Longitudinal Study.

Purpose This is a retrospective study of primary open-angle glaucoma patients treated with the immunosuppressor FK506 (tacrolimus) after an organ transplant. We assessed whether FK506 might be a potential neuroprotector adjuvant in glaucoma therapy. Patients and methods Organ transplant patients treated with FK506 for one or more years between 2006 and 2017 at the University of Texas Medical Branch (UTMB) were enrolled. Those selected were patients older than or equal to 50 years of age and had an ophthalmological eye examination with or without diagnostic tests for primary open-angle glaucoma (POAG). Sixty-one eligible subjects were included in the study and matched with the non-FK506 control group for age, gender, race, and follow-up visits. Results A lower incidence of POAG was noted in the FK506-treated patients (15%) when compared to the non-FK506 group (22%), though not significant (p=0.34). Among POAG subjects, the average retinal nerve fiber layer (RNFL) thickness decreased at a rate of 1.4 µm per year (p=0.0001) in the non-FK506 control patients versus 0.4 µm per year (p=0.34) in the FK506 patients. The superior and inferior RNFL quadrants in the control non-FK506 group had a thinning of 2.2 µm and 2.3 µm per year, respectively, (p=0.003 and p=0.0001), while in the FK506 patients, there was no significant loss. In addition, RNFL thinning in nasal and temporal quadrant also showed less reduction in FK506-treated subjects but was not statistically significant (p=0.68 and p=0.93). Conclusion FK506 therapy offers a new promising avenue for neuroprotection in POAG patients and needs to be investigated further for use in conjunction with conventional glaucoma treatments.

Opposite response of blood vessels in the retina to 6° head-down tilt and long-duration microgravity.

The Spaceflight Associated Neuro-ocular Syndrome (SANS), associated with the headward fluid shifts incurred in microgravity during long-duration missions, remains a high-priority health and performance risk for human space exploration. To help characterize the pathophysiology of SANS, NASA's VESsel GENeration Analysis (VESGEN) software was used to map and quantify vascular adaptations in the retina before and after 70 days of bed rest at 6-degree Head-Down Tilt (HDT), a well-studied microgravity analog. Results were compared to the retinal vascular response of astronauts following 6-month missions to the International Space Station (ISS). By mixed effects modeling, the trends of vascular response were opposite. Vascular density decreased significantly in the 16 retinas of eight astronauts and in contrast, increased slightly in the ten retinas of five subjects after HDT (although with limited significance). The one astronaut retina diagnosed with SANS displayed the greatest vascular loss. Results suggest that microgravity is a major variable in the retinal mediation of fluid shifts that is not reproduced in this HDT bed rest model.

Agreement for detecting glaucoma progression with the GDx guided progression analysis, automated perimetry, and optic disc photography.

PURPOSE: To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression. DESIGN: Observational cohort study. PARTICIPANTS: The study included 453 eyes from 252 individuals followed for an average of 46+/-14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy. METHODS: Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders. MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC(1) coefficient. RESULTS: Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC(1) coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44 (0.28-0.61), respectively. CONCLUSIONS: The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma.

Determinants of agreement between the confocal scanning laser tomograph and standardized assessment of glaucomatous progression.

PURPOSE: To estimate the agreement of confocal scanning laser tomograph (CSLT), topographic change analysis (TCA) with assessment of stereophotographs, and standard automated perimetry (SAP) for detecting glaucomatous progression and to identify factors associated with agreement between methods. DESIGN: Observational cohort study. PARTICIPANTS: We included 246 eyes of 167 glaucoma patients, glaucoma suspects, and ocular hypertensives. METHODS: We included CSLT series (n ≥ 4 tests; mean follow-up, 4 years), stereophotographs, and SAP results in the analysis. The number of progressors by guided progression analysis (GPA, "likely progression"), progressors by masked stereophotographs assessment and progressors by TCA as determined for 3 parameters related to the number of progressed superpixels within the disc margin was determined. Agreement between progression by each TCA parameter, stereophotographs and GPA was assessed using the Kappa test. Analysis of variance with post hoc analysis was applied to identify baseline factors including image quality (standard deviation of the mean topography), disc size and disease severity (pattern standard deviation [PSD] and cup area) associated with agreement/nonagreement between methods. MAIN OUTCOME MEASURES: Agreement in assessing glaucomatous progression between the methods including factors associated with agreement/nonagreement between methods. RESULTS: Agreement between progression by TCA and progression by stereophotographs and/or GPA was generally poor regardless of the TCA parameter and specificity cutoffs applied. For the parameters with the strongest agreement, cluster size in disc (CSIZE(disc)) and cluster area in disc (CAREA(disc)), kappa values were 0.16 (63.9%, agreement on 134 nonprogressing eyes and 23 progressing eyes) and 0.15 (64.1%, agreement on 135 nonprogressing eyes and 22 progressing eyes) at 99% cutoff. Most of the factors evaluated were not significantly associated with agreement/nonagreement between methods (all P > 0.07). However, SAP PSD was greater in the progressors by stereophotography only group compared with the progressors by TCA only group (5.8 ± 4.7 and 2.6 ± 2.2, respectively [P = 0.003] for CSIZE(disc) at 95% specificity and 5.4 ± 4.6 and 2.5 ± 2.3, respectively [P = 0.002] for CAREA(disc) at 99% specificity). CONCLUSIONS: Agreement for detection of longitudinal changes between TCA, stereophotography, and SAP GPA is poor. Progressors by stereophotography only tended to have more advanced disease at baseline than progressors by TCA only.

Cataract surgery and glaucoma.

PURPOSE OF REVIEW: To summarize the recent advances in the management of patients with coexisting cataract and glaucoma. RECENT FINDINGS: Although some evidence suggests that cataract surgery may be useful in the clinical management of eyes with angle closure glaucoma, recent studies show that the decrease in intraocular pressure (IOP) following cataract surgery alone in eyes with open angle glaucoma may be limited and transient. Combining cataract surgery with a trabeculectomy remains the preferred option. However, when IOP lowering is indicated, newer surgical techniques to lower IOP to be performed along with cataract extraction offer a promising alternative in patients with uncontrolled glaucoma and a visually significant cataract. SUMMARY: Cataract surgery alone or combined with trabeculectomy should be considered in the treatment of angle closure glaucoma. However, in eyes with open angle glaucoma, cataract surgery alone may be of limited clinical benefit in lowering IOP. Surgical alternatives to be combined with cataract extraction may be utilized to achieve a more significant IOP reduction. The appropriate treatment should be tailored based on patient's characteristics and the target IOP to be achieved.

Decreased Vascular Patterning in the Retinas of Astronaut Crew Members as New Measure of Ocular Damage in Spaceflight-Associated Neuro-ocular Syndrome.

Purpose: Ocular structural and functional changes, collectively termed spaceflight-associated neuro-ocular syndrome (SANS), have been described in astronauts undergoing long-duration missions in the microgravity environment of the International Space Station. We tested the hypothesis that retinal vascular remodeling, particularly by smaller vessels, mediates the chronic headward fluid shifts associated with SANS. Methods: As a retrospective study, arterial and venous patterns extracted from 30° infrared Heidelberg Spectralis retinal images of eight crew members acquired before and after six-month missions were analyzed with NASA's recently released VESsel GENeration Analysis (VESGEN) software. Output parameters included the fractal dimension and overall vessel length density that was further classified into large and small vascular branching generations. Vascular results were compared with SANS-associated clinical ocular measures. Results: Significant postflight decreases in Df, Lv, and in smaller but not larger vessels were quantified in 11 of 16 retinas for arteries and veins (P value for Df, Lv, and smaller vessels in all 16 retinas were ≤0.033). The greatest vascular decreases occurred in the only retina displaying clinical evidence of SANS by choroidal folds and optic disc edema. In the remaining 15 retinas, decreases in vascular density from Df and Lv ranged from minimal to high by a custom Subclinical Vascular Pathology Index. Conclusions: Together with VESGEN, the Subclinical Vascular Pathology Index may represent a new, useful SANS biomarker for advancing the understanding of SANS etiology and developing successful countermeasures for long duration space exploration in microgravity, although further research is required to better characterize retinal microvascular adaptations.

Neuronal Epac1 mediates retinal neurodegeneration in mouse models of ocular hypertension.

Progressive loss of retinal ganglion cells (RGCs) leads to irreversible visual deficits in glaucoma. Here, we found that the level of cyclic AMP and the activity and expression of its mediator Epac1 were increased in retinas of two mouse models of ocular hypertension. Genetic depletion of Epac1 significantly attenuated ocular hypertension-induced detrimental effects in the retina, including vascular inflammation, neuronal apoptosis and necroptosis, thinning of ganglion cell complex layer, RGC loss, and retinal neuronal dysfunction. With bone marrow transplantation and various Epac1 conditional knockout mice, we further demonstrated that Epac1 in retinal neuronal cells (especially RGCs) was responsible for their death. Consistently, pharmacologic inhibition of Epac activity prevented RGC loss. Moreover, in vitro study on primary RGCs showed that Epac1 activation was sufficient to induce RGC death, which was mechanistically mediated by CaMKII activation. Taken together, these findings indicate that neuronal Epac1 plays a critical role in retinal neurodegeneration and suggest that Epac1 could be considered a target for neuroprotection in glaucoma.

Diagnostic accuracy of pattern electroretinogram optimized for glaucoma detection.

PURPOSE: To assess the ability of the new pattern electroretinogram optimized for glaucoma detection (PERGLA) paradigm to discriminate between healthy individuals and individuals with glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. PARTICIPANTS: One hundred forty-two eyes of 71 participants (42 healthy and 29 with GON in at least 1 eye) enrolled in the University of California, San Diego, Diagnostic Innovations in Glaucoma Study were studied. Healthy individuals were those recruited as healthy with healthy-appearing optic disc by examination and masked stereoscopic optic disc photograph evaluation. Glaucomatous optic neuropathy was defined based on stereophotograph evaluation. METHODS: The PERGLA (Glaid Elettronica, Pisa, Italy) recordings were obtained within 6 months of standard automated perimetry (SAP) testing. Dependent variables were PERGLA amplitude, phase, amplitude asymmetry, phase asymmetry, and SAP pattern standard deviation (PSD) and mean deviation (MD). MAIN OUTCOME MEASURES: Diagnostic accuracy (sensitivity and specificity) of the PERGLA normative database for classifying healthy and glaucomatous individuals was determined. In addition, performance (areas under receiver operating characteristic curves [AUCs]) of PERGLA amplitude and phase for classifying healthy (n=84) and GON (n=50) eyes was determined. Results from both analyses were compared with those from SAP. RESULTS: Sensitivity and specificity of the PERGLA normative database were 0.76 and 0.59, respectively, compared with 0.83 and 0.77 for SAP. The AUCs for PERGLA amplitude and phase were 0.75 and 0.50 (chance performance), respectively. The AUCs for SAP PSD and MD were 0.83 and 0.78, respectively. CONCLUSIONS: Pattern electroretinograms recorded using the PERGLA paradigm can discriminate between healthy and glaucoma eyes, although this technique performed no better than SAP at this task. Low specificity of the PERGLA normative database suggests that the distribution of recordings included in the database is not ideal.

Clinicians agreement in establishing glaucomatous progression using the Heidelberg retina tomograph.

PURPOSE: To assess the degree of concordance among clinicians reviewing 3 Heidelberg retina tomograph (HRT) printouts used to detect progression, the Moorfields regression analysis (MRA), the topographic change analysis (TCA), and trend analysis (TA), and to compare with progression identified by stereophotographs. DESIGN: Observational cohort study. PARTICIPANTS: We longitudinally followed 237 eyes of 168 patients (50 glaucomatous eyes, 187 glaucoma suspects) from the Diagnostic Innovation in Glaucoma Study (mean follow-up, 46.8+/-14.2 months), with a minimum of 4 HRT images (range, 4-8). METHODS: Three experienced observers judged the presence of progression using the HRT follow-up printouts available for each HRT method of analysis (MRA, TCA, TA). The overall assessment was based on majority rule, with >or=2 graders agreeing on the classification. MAIN OUTCOME MEASURES: Observers agreement in assessing HRT progression and agreement for progression or no progression between the HRT methods of analysis and the reference standard represented by masked stereophotograph assessment. The kappa test was used to assess the interobserver agreement. RESULTS: In general, agreement among clinicians for subjective assessment of progression based on HRT printouts was moderate to good; agreement (kappa) ranged from 0.52 to 0.71 for MRA, 0.61 to 0.63 for TCA, and 0.45 to 0.74 for TA. Of the 237 eyes, 16 (6.8%) were found to progress during follow-up based on masked stereophotograph assessment. Agreement for progression/no progression between the HRT methods and stereophotography was similar among MRA (84.8%, agreement on 5 progressing eyes and 196 nonprogressing eyes; kappa = 0.14), TCA, (82.3%, agreement on 8 progressing eyes and 187 nonprogressing eyes; kappa = 0.2), and TA (84%, agreement on 2 progressing eyes and 197 nonprogressing eyes; kappa = 0.01). CONCLUSIONS: Clinicians' agreement in identifying suspected glaucomatous progression using different HRT methods of analysis was moderate to good and was similar among all methods, including MRA, which is not designed to detect progression. Agreement between progression identified by HRT and masked stereophotograph assessment was poor. These results suggest that assessment of the HRT and stereophotography may be identifying different aspects of structural change. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Relationship of the 24-hour pattern of intraocular pressure with optic disc appearance in primary open-angle glaucoma.

PURPOSE: To study the relationship between the 24-hour pattern of intraocular pressure (IOP) with optic disc appearance in primary open-angle glaucoma (POAG) patients. DESIGN: Observational clinical study. PARTICIPANTS: Seventy-five eyes of 45 POAG patients. METHODS: Patients underwent 24-hour IOP assessment in a sleep laboratory. Two observers classified the optic disc appearance for each eye as either concentric or nonconcentric. The IOP measurements were obtained with the subjects in the supine and sitting positions during the diurnal period and in the supine position during the nocturnal period. The mean, peak, and trough IOP and IOP range (peak through trough) were calculated for the office-hour period (9 am to 4 pm), the diurnal period (7 am to 11 pm), the nocturnal period (11 pm to 7 am), and the 24-hour period. Further, the difference in supine and sitting IOP during the diurnal periods was calculated, and generalized estimating equations were used to compare IOP measurements in both groups. MAIN OUTCOME MEASURES: Diurnal and nocturnal IOP measurements. RESULTS: Forty eyes were classified as having concentric optic disc appearance and 35 eyes as having nonconcentric optic disc appearance. The mean nocturnal IOP was significantly greater in the concentric group (mean+/-standard deviation [SD], 24.0+/-3.8 mmHg) compared with the nonconcentric group (mean+/-SD, 21.9+/-1.9 mmHg; P = 0.004). Most IOP peaks of patients with the concentric optic disc appearance occurred during the nocturnal period, as opposed to the diurnal period of patients with the nonconcentric optic disc appearance. CONCLUSIONS: Concentric optic disc appearance may be associated with higher nocturnal IOP compared with nonconcentric optic disc appearance. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Effect of image quality on tissue thickness measurements obtained with spectral domain-optical coherence tomography.

The purpose of this study was to investigate the effect of image quality on retinal nerve fiber layer (RNFL) and retinal thickness measurements obtained using three commercially available spectral domain-optical coherence tomographers (SD-OCT). Subjectively determined good, medium and poor quality images were obtained from four healthy and one glaucoma suspect eyes. RNFL and retinal thickness measurements were compared as a function of image quality. Results indicate that when image quality is within the range specified as acceptable by SD-OCT manufacturers, RNFL and retinal thickness measurements are comparable.

Spectral domain-optical coherence tomography to detect localized retinal nerve fiber layer defects in glaucomatous eyes.

This study examines the ability of RTVue, Cirrus and Spectralis OCT Spectral domain-optical coherence tomographs (SD-OCT) to detect localized retinal nerve fiber layer defects in glaucomatous eyes. In this observational case series, four glaucoma patients (8 eyes) were selected from the University of California, San Diego Shiley Eye Center and the Diagnostic Innovations in Glaucoma Study (DIGS) based on the presence of documented localized RNFL defects in at least one eye confirmed by masked stereophotograph assessment. One RTVue 3D Disc scan, one RTVue NHM4 scan, one Cirrus Optic Disk Cube 200x200 scan and one Spectralis scan centered on the optic disc (15x15 scan angle, 768 A-scans x 73 B-scans) were obtained on all undilated eyes within a single session. Results were compared with those obtained from stereophotographs. In 6 eyes the presence of localized RNFL defects was detected by stereophotography. In general, by qualitatively evaluating the retinal thickness maps generated, all SD-OCT instruments examined were able to confirm the presence of localized glaucomatous structural damage seen on stereophotographs. This study confirms SD-OCT is a promising technology for glaucoma detection as it may assist clinicians identify the presence of localized glaucomatous structural damage.