Elmira Baghdasaryan

Outcomes after Descemet stripping endothelial keratoplasty in glaucoma patients with previous trabeculectomy and tube shunt implantation.

Purpose: To describe the incidence of intraoperative and postoperative complications and visual outcomes in eyes with previous penetrating glaucoma surgery undergoing Descemet stripping endothelial keratoplasty (DSEK). Methods: A retrospective review of the first 227 cases of DSEK performed by 2 surgeons at a single institution. Data were collected regarding the performance of concurrent ocular procedures, intraoperative complications, postoperative visual outcomes, and postoperative complications, including primary graft failure, donor dislocation, endothelial rejection, and intraocular pressure (IOP) elevation. Results: Fifty-six of the 227 DSEK procedures were performed in 52 eyes with previous trabeculectomy and/or tube shunt implantation. The percentage of procedures performed in eyes with and without a history of penetrating glaucoma surgery that resulted in primary graft failure (5.4% vs. 4.1%; P = 0.71) and donor dislocation (12.5% vs. 15.2%; P = 0.83) were not statistically significantly different. Additionally, the endothelial rejection rate was not significantly different between cases performed in eyes with (1/19.2 eye-years) and without (1/20.1 eye-years) a history of glaucoma surgery (P = 0.99). The incidence of elevated IOP (≥25 mm Hg) after DSEK was the highest in eyes with medically controlled glaucoma (47.4%), followed by eyes without a history of glaucoma (18.3%), and was the lowest in eyes with previous glaucoma surgery (11.5%). Postoperative corrected distance visual acuity was improved over the preoperative corrected distance visual acuity in 81%, 95%, and 88% of eyes with previous glaucoma surgery, medically controlled glaucoma, and no glaucoma, respectively. Conclusions: DSEK is an effective procedure to improve vision in the majority of eyes with advanced glaucoma after trabeculectomy and/or tube shunt implantation. The incidence of postoperative complications, such as donor dislocation, primary graft failure, and endothelial rejection, is not significantly higher in eyes with a history of glaucoma surgery before DSEK. Because almost 50% of eyes with medically controlled glaucoma before DSEK experienced IOP elevation after surgery, careful monitoring of the IOP after DSEK is especially important in this patient population.

Repeatability and Reproducibility of Superficial Macular Retinal Vessel Density Measurements Using Optical Coherence Tomography Angiography En Face Images

Importance The repeatability and reproducibility of quantitative metrics from optical coherence tomographic angiography (OCTA) must be assessed before these data can be confidently interpreted in clinical research and practice. Objective To evaluate the repeatability and reproducibility of OCTA-derived retinal vascular quantitative metrics. Design, Setting and Participants In this cross-sectional study, 21 healthy volunteers (42 eyes) and 22 patients with retinal disease (22 eyes), including 14 with age-related macular degeneration, 3 with epiretinal membrane, 2 with diabetic retinopathy, 2 with myopic macular degeneration, and 1 with retinal vein occlusion, were enrolled. Participants were recruited from September 1 through November 31, 2016. Each eye underwent 3 repeated scans with 3 instruments for a total of 9 acquisitions. Eyes were randomly assigned to scanning with a 3 × 3-mm or 6 × 6-mm pattern. Eyes were excluded from subsequent analysis if any acquisition had a signal strength of less than 7. Repeatability (defined as the agreement in measurements within a device) and reproducibility (defined as the agreement between devices of the same type) were assessed by intraclass correlation coefficient (ICC) and coefficient of variation. Exposures All eyes underwent scanning using 3 separate devices. Main Outcomes and Measures Vessel length density (VLD) and perfusion density (PD) of the superficial retinal vasculature. Results A total of 21 healthy volunteers (8 men and 13 women; mean [SD] age, 36 [6] years) and 22 patients with retinal disease (15 men and 7 women; mean [SD] age, 79 [9] years) underwent evaluation. Of these, 40 of 42 normal eyes and 15 of 22 eyes with retinal disease met signal strength criteria and were included in this analysis. The ICC among the 3 consecutive scans ranged from 0.82 to 0.98 for VLD and from 0.83 to 0.95 for PD. The coefficient of variation (CV) ranged from 2.2% to 5.9% for VLD and from 2.4% to 5.9% for PD. For reproducibility, the ICC ranged from 0.62 to 0.95 and the CV was less than 6% in all groups. The agreement was highest for the 3 × 3-mm pattern in the inner ring (ICC range, 0.92 [95% CI, 0.85-0.96] to 0.96 [95% CI, 0.93-0.98]) and 6 × 6-mm pattern in the outer ring (ICC range, 0.93 [95% CI, 0.86-0.97] to 0.96 [95% CI, 0.92-0.98]). Conclusions and Relevance Vessel length density and PD of the superficial retinal vasculature can be obtained from OCTA images with high levels of repeatability and reproducibility but can vary with scan pattern and location.

cGAS drives noncanonical-inflammasome activation in age-related macular degeneration

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D–dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.

Choriocapillaris Imaging Using Multiple En Face Optical Coherence Tomography Angiography Image Averaging

Importance Imaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging. Objective To investigate multiple en face image averaging on OCTA images of the choriocapillaris. Design, Setting, and Participants Observational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study. The study dates were August to September 2016. Exposures All participants underwent OCTA imaging of the macula covering a 3 × 3-mm area using OCTA software (Cirrus 5000 with AngioPlex; Carl Zeiss Meditec). One eye per participant was repeatedly imaged to obtain 9 OCTA cube scan sets. Registration was first performed using superficial capillary plexus images, and this transformation was then applied to the choriocapillaris images. The 9 registered choriocapillaris images were then averaged. Quantitative parameters were measured on binarized OCTA images and compared with the unaveraged OCTA images. Main Outcome and Measure Vessel caliber measurement. Results Seventeen eyes of 17 participants (mean [SD] age, 35.1 [6.0] years; 9 [53%] female; and 9 [53%] of white race/ethnicity) with sufficient image quality were included in this analysis. The single unaveraged images demonstrated a granular appearance, and the vascular pattern was difficult to discern. After averaging, en face choriocapillaris images showed a meshwork appearance. The mean (SD) diameter of the vessels was 22.8 (5.8) µm (range, 9.6-40.2 µm). Compared with the single unaveraged images, the averaged images showed more flow voids (1423 flow voids [95% CI, 967-1909] vs 1254 flow voids [95% CI, 825-1683], P < .001), smaller average size of the flow voids (911 [95% CI, 301-1521] µm2 vs 1364 [95% CI, 645-2083] µm2, P < .001), and greater vessel density (70.7% [95% CI, 61.9%-79.5%] vs 61.9% [95% CI, 56.0%-67.8%], P < .001). The distribution of the number vs sizes of the flow voids was skewed in both unaveraged and averaged images. A linear log-log plot of the distribution showed a more homogeneous distribution in the averaged images compared with the unaveraged images. Conclusions and Relevance Multiple en face averaging can improve visualization of the choriocapillaris on OCTA images, transforming the images from a granular appearance to a level where the intervascular spaces can be resolved in healthy volunteers.

Descemet stripping endothelial keratoplasty after Ophtec 311 iris reconstruction lens implantation.

Purpose: To describe the variations in intraoperative technique, postoperative complications, and visual outcomes associated with Descemet stripping endothelial keratoplasty (DSEK) after Ophtec iris reconstruction lens implantation. Design: Retrospective, interventional, consecutive case series. Participants: Patients who underwent DSEK after Ophtec 311 iris reconstruction lens implantation at the Jules Stein Eye Institute, University of California, Los Angeles. Methods: Medical records were reviewed for demographic information, ophthalmic history, DSEK surgical technique, and postoperative clinical course. Main Outcome Measures: Intraoperative and postoperative complications and visual outcomes. Results: Four patients were identified (1 man and 3 women, age: 43-78). Three of the eyes had undergone prior penetrating keratoplasty (PKP), and each of the eyes had a history of glaucoma, with previous glaucoma surgery having been performed in 2 of the eyes. No intraoperative complications were encountered during the procedures, although an unplanned anterior vitrectomy was required in a previously vitrectomized eye. In each case, a complete air fill of the globe was obtained to ensure adherence of the donor button, and in 3 of the 4 cases, the donor button was sutured to the recipient cornea to prevent potential posterior dislocation. None of the cases developed donor button dislocation or primary graft failure. Corrected distance visual acuities improved to 20/40-20/160, corresponding to a mean improvement of 0.25 (range, 0.12-0.40), limited by irregular corneal astigmatism and advanced glaucomatous optic neuropathy. During a mean follow-up period of 15.6 months (range, 4.9-24.8 months), graft rejection developed in 2 of the 3 eyes with a history of endothelial rejection after PKP (0.42 episode per eye-year). Both of these eyes developed secondary graft failure, which also developed 14 months after DSEK in the other eye with a history of PKP failure before DSEK. Conclusions: DSEK can be successfully performed in eyes with partial or complete aniridia, such as those after Ophtec iris reconstruction lens implantation. Modifications to the standard DSEK technique increase the probability of successful donor adherence and decrease the risk of posterior dislocation of the donor corneal button. However, endothelial rejection may occur at an increased frequency, resulting in secondary graft failure.

Elevated Intraocular Pressure is a Common Complication During Active Microbial Keratitis

PURPOSE To determine the incidence, risk factor, and outcomes of elevated intraocular pressure (IOP) during active microbial keratitis. DESIGN Retrospective cohort study. METHODS One hundred eighty-four patients with culture-proven microbial keratitis examined from January 2003 through December 2007 were included. High IOP was defined as IOP of 22 mm Hg or higher measured during the episode of active keratitis. The control group consisted of eyes with microbial keratitis whose IOP remained less than 22 mm Hg. Twelve factors were evaluated by univariate and multivariate analyses to determine whether any were associated with increased IOP. The incidence, risk factors, microbial profile, the necessity of therapeutic surgery, time to resolution, and final visual acuity were compared between the high IOP group and the control group. RESULTS High IOP (mean, 29.1 mm Hg; range, 22 to 51 mm Hg) occurred in 52 (28%) of 184 patients with active corneal infection. Prior ocular surgery, diabetes mellitus, and ulcer size of 4.0 mm or larger were associated with IOP elevation (P ≤ .013). Surgical interventions were necessary in 19 (39%) of 49 patients in the high IOP group and in 14 (11%) of 129 patients in the control group (P < .0001). Time to ulcer resolution was longer in the high IOP group (mean, 50.1 ± 53.2 days) than in the control (mean, 31.6 ± 42.0 days; P = .005). Final visual acuity of 20/40 or better was achieved by more patients in the control group (47%) than in the high IOP group (20%; P < .001). CONCLUSIONS Elevated IOP was detected in a significant proportion of patients with active microbial keratitis and was associated with poorer outcomes. Routine IOP check should be performed to avoid possible optic nerve damage.

Reproducibility of Central Corneal Thickness Measurements in Normal Eyes Using the Zeiss Cirrus 5000 HD-OCT and Pentacam HR

Objectives: To determine the repeatability and reproducibility of Central Corneal Thickness (CCT) measurements using two different anterior segment imaging modalities, including those obtained with the new anterior segment lens attachments for the Cirrus 5000 HD-OCT. Methods: A total of 32 eyes from 16 normal volunteers (8 male, 8 female) were enrolled in this prospective study. CCT was measured by the same examiner using the Cirrus 5000 HD-OCT and Pentacam HR. The results of CCT obtained by each method were averaged and compared using t-test analysis. The agreement between the measurement methods was evaluated. Coefficient of Repeatability (CoR) and Intra-Class Correlation Coefficient (ICC) were computed. Results: The mean measurements taken with the Cirrus OCT anterior chamber lens (CCTAC), HD cornea lens (CCTHDC) and pachymetry scans (CCTPach) were 545.35 ± 31.02, 537.87 ± 26.82, and 532.04 ± 29.82 µm, respectively. The mean CCT obtained with the Pentacam (CCTPent) was 545.51 ± 30.71 µm. CCTPent were significantly higher than CCTHDC and CCTPach (p< 0.0001). In contrast, the CCTPent and CCTAC were similar (p=0.87). CCT, as evaluated by the two different instruments, showed excellent correlation (r > 0.98, p< 0.0001) with an ICC > 0.99 (95% CI, 0.97 – 0.99). CoR was the highest for CCTPach (3.7 ± 1.4, 95% CI (3.0- 4.6)). Conclusion: CCT measurements from the Cirrus OCT using the new anterior segment lens attachments and the Pentacam HR are highly correlated. This should allow the use of a standardized correction factor if necessary to inter-relate the measurements between the two devices.

Assessment of Corneal Changes Associated with Topical Antiglaucoma Therapy Using in vivo Confocal Microscopy

Purpose: Ocular surface disease (OSD) is highly prevalent in eyes treated with chronic, topical antiglaucoma (A/G) therapy. The purpose of this study was to utilize in vivo confocal microscopy (IVCM) to evaluate the corneal morphology, including characteristics of corneal epithelial cells, presence of epithelial dendritic cells (DCs), and characteristics of subbasal nerve plexus, of eyes under topical A/G therapy versus normal eyes. Methods: Central corneal images were prospectively captured from 30 eyes of 16 patients under topical A/G therapy (>6 months) and 20 normal control eyes, using IVCM (HRT 3 RCM, Heidelberg, Germany). Demographic data were collected, as well as information on the types and duration of A/G therapy. In addition, OSD index (OSDI) score, tear film breakup time, Schirmer 1 test results, density of epithelial wing cells (WCs) and basal cells (BCs), subbasal nerve features (density, tortuosity, and reflectivity), and presence of DCs were all assessed and recorded by trained Doheny Image Reading Center graders. Results: IVCM findings of 30 glaucomatous eyes and 20 normal control eyes were analyzed. The mean OSDI score was 8.72 in controls and 32.06 in patients under A/G therapy (p = 0.002). Nerve fiber density, nerve fiber reflectivity, and BC density were all decreased in the A/G group (1,789.07 ± 785.70 μm/frame, 2.79 ± 0.83, 6,457.67 ± 692.55 cells/mm2, respectively) as compared to controls (2,815.981 ± 563.77 μm/frame, 3.52 ± 0.50, 7,854.13 ± 1,073.69 cells/mm2, respectively) (p < 0.05), whereas the decrease in WC density was statistically nonsignificant (p = 0.5). Nerve tortuosity and DC density were both significantly greater in the A/G eyes (3.00 ± 0.57, 71.24 ± 61.74 cells/mm2, respectively) compared to controls (2.10 ± 0.42, 34.08 ± 11.70 cells/mm2, respectively) (p < 0.05). Tear film breakup time and Schirmer 1 test results were significantly lower in the A/G group as compared to controls (p < 0.001). Conclusions: Using IVCM, our study identified significant microstructural alterations in the corneas of eyes treated with topical A/G therapy. In addition, our study also revealed that glaucoma patients treated with topical A/G therapy report significantly higher OSDI scores compared to controls. Thus, IVCM may be a useful tool in providing structural parameters to correlate with the functional OSDI assessments in the evaluation of ocular surface toxicity associated with topical A/G therapy.

Analysis of ocular inflammation in anterior chamber—involving uveitis using swept-source anterior segment OCT

AbstractPurposeTo evaluate the utility of swept-source (SS) optical coherence tomography (OCT) to objectively analyze the degree of anterior chamber (AC) inflammation.MethodsThirty-eight eyes of 32 patients with uveitis and 20 control eyes were enrolled. SS OCT B-scans were obtained, and the number of cells in the B-scans was counted using two methods: (1) manual grading by Point Picker plug-in of Image J (http://bigwww.epfl.ch/thevenaz/pointpicker/) and (2) automated grading by the Image J Particle Analysis algorithm (http://imagej.net/Particle_Analysis). The automated and manual AC cell counts were correlated with the Standardization of Uveitis Nomenclature score. ResultsThe average numbers of AC inflammatory cells counted by the automated method were 8 ± 4.0, 18 ± 3.0, 42 ± 14.0, 81 ± 32.0, 117 ± 57.0, and 275 ± 67.0 cells/mm2 for grades 0, 0.5 + , 1 + , 2 + , 3 + , and 4 + , respectively. For the same clinical categories, the average manual cell counts were 6 ± 4.0, 18 ± 3.0, 34 ± 14.0, 72 ± 32.0, 92 ± 43.0, and 168 ± 65.0 cells/mm2, respectively. Zero cells were detected in the AC of healthy eyes. The automated and manual methods were highly correlated (R = 0.98, p < 0.001) and showed good correlation with the clinical grading (R = 0.88, p < 0.001). A mean AC particle size of 117.4 ± 108.8 μm was obtained by the automated method.ConclusionsQuantification of the AC cells imaged by SS AS-OCT shows good correlation with categorical clinical severity assessments in uveitis eyes. This approach may provide a more objective method for monitoring uveitis and response to uveitis therapy.

Multiple enface image averaging for enhanced optical coherence tomography angiography imaging

To investigate the effect of multiple enface image averaging on image quality of the optical coherence tomography angiography (OCTA).