Theodore Leng

The chick chorioallantoic membrane as a model tissue for surgical retinal research and simulation.

Purpose: We describe the use of chick chorioallantoic membrane (CAM) as a model system for the study of the precision and safety of vitreoretinal microsurgical instruments and techniques. Methods: The CAM was prepared for experimentation with and without its inner shell membrane (ISM) attached for in vivo and in vitro experiments that simulated medical and surgical interventions on the retina. Results: The CAM’s ease of use, low cost, and anatomic structure make it a convenient model for surgical retinal and retinal vascular modeling. Conclusion: While CAM has been used extensively in the past for ocular angiogenesis studies, we describe the tissue as a useful tool for a variety of other applications, including (1) testing of novel surgical tools and techniques for cutting and coagulating retina and its vasculature, (2) testing vessel cannulation and injection techniques, (3) angiographic studies, and (4) endoscopic surgery.

Quantitative SD-OCT Imaging Biomarkers as Indicators of Age-Related Macular Degeneration Progression

PURPOSE We developed a statistical model based on quantitative characteristics of drusen to estimate the likelihood of conversion from early and intermediate age-related macular degeneration (AMD) to its advanced exudative form (AMD progression) in the short term (less than 5 years), a crucial task to enable early intervention and improve outcomes. METHODS Image features of drusen quantifying their number, morphology, and reflectivity properties, as well as the longitudinal evolution in these characteristics, were automatically extracted from 2146 spectral-domain optical coherence tomography (SD-OCT) scans of 330 AMD eyes in 244 patients collected over a period of 5 years, with 36 eyes showing progression during clinical follow-up. We developed and evaluated a statistical model to predict the likelihood of progression at predetermined times using clinical and image features as predictors. RESULTS Area, volume, height, and reflectivity of drusen were informative features distinguishing between progressing and nonprogressing cases. Discerning progression at follow-up (mean, 6.16 months) resulted in a mean area under the receiver operating characteristic curve (AUC) of 0.74 (95% confidence interval [CI], 0.58, 0.85). The maximum predictive performance was observed at 11 months after a patients first early AMD diagnosis, with mean AUC 0.92 (95% CI, 0.83, 0.98). Those eyes predicted to progress showed a much higher progression rate than those predicted not to progress at any given time from the initial visit. CONCLUSIONS Our results demonstrate the potential ability of our model to identify those AMD patients at risk of progressing to exudative AMD from an early or intermediate stage.

Reducing oral flora contamination of intravitreal injections with face mask or silence.

Purpose: To provide experimental evidence to support or refute the proposition that the use of surgical face masks and/or avoidance of talking can decrease the dispersion of respiratory flora during an intravitreal injection. Methods: Ten surgeons recited a 30-second standardized script with blood agar plates positioned 30 cm below their mouths. The plates were divided into 4 groups, with 10 plates per group. In Group 1, participants did not wear a face mask. In Group 2, participants wore a standard surgical mask. In Group 3, no mask was worn, but plates were pretreated with 5% povidone–iodine. In Group 4, no mask was worn, and participants remained silent for 30 seconds. The plates were then incubated at 37°C for 24 hours, and the number of colony-forming units (CFUs) was determined. Results: Mean bacterial growth were as follows: Group 1, 8.6 CFUs per subject; Group 2, 1.1 CFUs per subject; Group 3, 0.1 CFUs per subject; and Group 4, 2.4 CFUs per subject. Differences between the groups were statistically significant (P < 0.05), with the exception of Group 2 versus Group 4 (P = 0.115). Conclusion: The use of a face mask and avoidance of talking each significantly decreased the dispersion of bacteria. Even without these interventions, plates pretreated with povidone–iodine demonstrated the least bacterial growth.

Automated drusen segmentation and quantification in SD-OCT images

Spectral domain optical coherence tomography (SD-OCT) is a useful tool for the visualization of drusen, a retinal abnormality seen in patients with age-related macular degeneration (AMD); however, objective assessment of drusen is thwarted by the lack of a method to robustly quantify these lesions on serial OCT images. Here, we describe an automatic drusen segmentation method for SD-OCT retinal images, which leverages a priori knowledge of normal retinal morphology and anatomical features. The highly reflective and locally connected pixels located below the retinal nerve fiber layer (RNFL) are used to generate a segmentation of the retinal pigment epithelium (RPE) layer. The observed and expected contours of the RPE layer are obtained by interpolating and fitting the shape of the segmented RPE layer, respectively. The areas located between the interpolated and fitted RPE shapes (which have nonzero area when drusen occurs) are marked as drusen. To enhance drusen quantification, we also developed a novel method of retinal projection to generate an en face retinal image based on the RPE extraction, which improves the quality of drusen visualization over the current approach to producing retinal projections from SD-OCT images based on a summed-voxel projection (SVP), and it provides a means of obtaining quantitative features of drusen in the en face projection. Visualization of the segmented drusen is refined through several post-processing steps, drusen detection to eliminate false positive detections on consecutive slices, drusen refinement on a projection view of drusen, and drusen smoothing. Experimental evaluation results demonstrate that our method is effective for drusen segmentation. In a preliminary analysis of the potential clinical utility of our methods, quantitative drusen measurements, such as area and volume, can be correlated with the drusen progression in non-exudative AMD, suggesting that our approach may produce useful quantitative imaging biomarkers to follow this disease and predict patient outcome.

Delayed-onset bleb-associated endophthalmitis (1996-2008): Causative organisms and visual acuity outcomes

Purpose: The purpose of this study was to report the clinical features, organisms, and outcomes of patients with delayed-onset bleb-associated endophthalmitis. Methods: Retrospective consecutive case series. Patients who were treated for delayed-onset bleb-associated endophthalmitis between January 1, 1996, and July 1, 2008, at a single institution were included. Information on visual acuities, clinical characteristics, causative organisms, and treatment outcomes were collected. Infections within 1 month of glaucoma filtering surgery, inadvertent filtering blebs after cataract surgery, and patients with glaucoma drainage devices were excluded. Results: A total of 71 eyes from 68 patients were identified. An adjunctive antifibrotic agent was used in 48 eyes (68%). The mean time between surgery and endophthalmitis was 4.8 years (range, 0.1-16; standard deviation, 3.6). The average follow-up time after initial treatment was 37 months (range 1-144; standard deviation, 41). At presentation, 17 eyes (24%) had a bleb leak. Fifty-seven eyes (83%) were culture positive. The most common causative organisms were Streptococcus species in 20 eyes (30%), gram-negative organisms in 19 eyes (28%), and coagulase-negative Staphylococcus in 12 eyes (18%). All gram-positive isolates were sensitive to vancomycin. Nine eyes (13%) eventually underwent evisceration or enucleation secondary to pain and/or poor vision. The main outcome measure was best-corrected visual acuity at the last follow-up examination. Final visual acuities in the initial tap/inject group (n = 45) versus the initial vitrectomy group (n = 24) were as follows: ≥20/40 (29% vs. 4.2%), 20/50 to 20/400 (36% vs. 29%), and <5/200 (36% vs. 62%). Conclusion: Streptococcus species and gram-negative organisms were the most common causative isolates identified in this case series of delayed-onset bleb-associated endophthalmitis. Despite treatment of the infection, visual outcomes were generally poor.

Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): five years of screening with telemedicine.

BACKGROUND AND OBJECTIVE To report the 5-year results of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative. PATIENTS AND METHODS Infants requiring retinopathy of prematurity (ROP) screening at six neonatal intensive care units from December 1, 2005, to November 30, 2010, were evaluated with remote retinal photography by an ROP specialist. Every infant received outpatient binocular indirect ophthalmoscope examinations until termination criteria were achieved or until treatment. Outcomes were treatment-warranted ROP (TW-ROP, ETROP type 1) and adverse anatomical events. RESULTS Five hundred eleven infants (1,022 eyes) were screened. Fifteen infants had TW-ROP and underwent laser photocoagulation. The TW-ROP cohort had significantly lower birth weight and gestational age (both P < .001). No patient progressed to adverse anatomical outcomes and no case of TW-ROP was missed. Tele-medicine had 100% sensitivity, 99.8% specificity, 93.8% positive predictive value, and 100% negative predictive value for detection of TW-ROP. CONCLUSION Telemedicine demonstrates high diagnostic accuracy for detection of TW-ROP and can complement ROP screening.

SUNDROP: six years of screening for retinopathy of prematurity with telemedicine

OBJECTIVE To report the 6-year results of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative in the context of telemedicine screening initiatives for retinopathy of prematurity (ROP). DESIGN A retrospective analysis. PARTICIPANTS Premature newborns requiring ROP screening at 6 neonatal intensive care units from December 1, 2005, to November 30, 2011. METHODS Infants were evaluated via remote retinal photography by an ROP specialist. A total of 608 preterm infants meeting ROP examination criteria were screened with the RetCam II/III (Clarity Medical Systems, Pleasanton, Calif.). Primary outcomes were treatment-warranted ROP (TW-ROP) and adverse anatomical events. RESULTS During the 6 years, 1216 total eyes were screened during 2169 examinations, generating 26 970 retinal images, an average of 3.56 examinations and 44.28 images per patient. Twenty-two (3.6%) of the infants screened met criteria for TW-ROP. Compared with bedside binocular ophthalmoscopy, remote interpretation of RetCam II/III images had a sensitivity of 100%, specificity of 99.8%, positive predicative value of 95.5%, and negative predicative value of 100% for the detection of TW-ROP. No adverse anatomical outcomes were observed for any enrolled patient. CONCLUSIONS The 6-year results for the SUNDROP telemedicine initiative were highly favourable with respect to diagnostic accuracy. Telemedicine appears to be a safe, reliable, and cost-effective complement to the efforts of ROP specialists, capable of increasing patient access to screening and focusing the resources of the current ophthalmic community on infants with potentially vision-threatening disease.

Intraoperative use of three-dimensional spectral-domain optical coherence tomography.

BACKGROUND AND OBJECTIVE To develop a prototype three-dimensional anterior segment spectral-domain optical coherence tomography (SD-OCT) device and demonstrate the feasibility of its use in the operating room. PATIENTS AND METHODS Single-institution interventional case series including six consecutive patients undergoing Descemets stripping automated endothelial keratoplasty (DSAEK). The prototype anterior segment SD-OCT was used intraoperatively to search for the presence of interface fluid between the host cornea and the DSAEK graft. RESULTS Anterior segment SD-OCT was successfully used intraoperatively during DSAEK. After the initial placement of the graft, no fluid was clinically apparent; however, interface fluid was identified by anterior segment SD-OCT in two of the six cases. After additional aspiration, all patients were fluid-free on follow-up anterior segment SD-OCT scanning. CONCLUSION Intraoperative anterior segment SD-OCT was used successfully to find interface fluid that was clinically undetectable under the microscope. As such, all patients were able to leave the operating room with a fully attached graft.

Spectral domain optical coherence tomography characteristics of cuticular drusen

Purpose: To evaluate the appearance of cuticular drusen with spectral domain optical coherence tomography. Methods: Eyes of patients with cuticular drusen were imaged using a prototype spectral domain optical coherence tomography instrument with 5-μm axial resolution. Thickness maps were obtained after automated segmentation of the internal limiting membrane and retinal pigment epithelium layers using a proprietary algorithm. The volume of subretinal fluid (SRF) was calculated using a manual segmentation technique that involved drawing boundaries around the SRF. The repeatability of these measurements was tested by comparing the volume measurements from multiple scans performed on the same day in four eyes of three patients. Results: Sixteen eyes from eight patients with cuticular drusen were scanned. Areas of decreased retinal thickness overlying drusen were best visualized using the three-dimensional retinal thickness map. The distribution and sawtooth pattern of cuticular drusen were best visualized using three-dimensional retinal pigment epithelium segmentation. Of the 16 eyes, 13 had SRF within the macula. In the eyes with macular SRF, characteristic excrescences were present along the outer retina and attenuation of the photoreceptor inner and outer segment boundary were observed in many areas. In areas where the retina was detached, the retinal pigment epithelium–Bruchs membrane complex appeared nodular or attenuated. The volumetric measurements of the SRF were performed using a manual segmentation with a 1.11% mean difference between repeated measurements on the same day (range, 0.47–1.68%; standard deviation, 0.55%). Conclusion: The sawtooth pattern of drusen and the presence of excrescences along the detached outer retina are characteristic features of cuticular drusen that should be helpful in confirming the diagnosis of this condition. The volumetric analysis of the SRF is repeatable and may be useful in following the clinical course of these patients.

Selective retinal therapy with microsecond exposures using a continuous line scanning laser.

Purpose: To evaluate the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser. Methods: A 532-nm Nd:YAG laser (PASCAL) with retinal beam diameters of 40 μm and 66 μm was applied to 60 eyes of 30 Dutch-belted rabbits. Retinal exposure duration varied from 15 μs to 60 μs. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography. Retinal pigment epithelial (RPE) flatmounts were evaluated with live-dead fluorescent assay. Histological analysis was performed at 7 time points from 1 hour to 2 months. Results: The ratios of the threshold of rupture and of ophthalmoscopic visibility to fluorescein angiography visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Fluorescein angiography and live-dead fluorescent assay yielded similar thresholds of RPE damage. Above the ophthalmoscopic visibility threshold, histology showed focal RPE damage and photoreceptor loss at 1 day, without inner retinal effects. By 1 week, photoreceptor and RPE continuity was restored. By 1 month, photoreceptors appeared normal. Conclusion: Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors without permanent scarring or inner retinal damage. Continuous scanning laser can treat large retinal areas within standard eye fixation time.