Alex Yuan

Evaluation of choroidal thickness in retinitis pigmentosa using enhanced depth imaging optical coherence tomography

Objective To describe the choroidal characteristics of patients with retinitis pigmentosa (RP) using enhanced depth imaging (EDI) and spectral domain (SD) optical coherence tomography (OCT). Purpose To investigate the spectral-domain ocular coherence tomography features of the choroid in patients with RP using EDI. Methods A prospective, case–control study of 21 patients from the Cole Eye Institute with RP imaged using the Spectralis OCT and an EDI protocol. Submacular choroidal thickness measurements were obtained beneath the fovea and at 500 µm intervals for 2.5 mm nasal and temporal to the centre of the fovea. These measurements were compared to choroidal thickness measurements from 25 healthy age-matched controls with similar refractive error range and no clinical evidence of retinal or glaucomatous disease. Statistical analysis was performed to compare choroidal thickness at each location between the two groups and to correlate choroidal thickness with best-corrected visual acuity and central retinal thickness. Results Mean ages were 40.6 years for control patients and 45.1 years for RP patients (p>0.05). Mean choroidal thickness measurements were 245.6±103 µm in RP patients and 337.8.2±109 µm in controls (p<0.0001). There was no correlation between subfoveal choroidal thickness and visual acuity or retinal thickness in the RP patients when compared to the control group. Conclusions Submacular choroidal thickness, as measured by SD–OCT EDI, is significantly reduced in patients with RP, but did not correlate with visual acuity or retinal thickness in RP patients. Further research is needed to understand better the pathophysiological significance of the choroidal alterations present in RP.

Intrasurgical assessment of subretinal tPA injection for submacular hemorrhage in the PIONEER study utilizing intraoperative OCT.

BACKGROUND AND OBJECTIVE To assess the feasibility of intraoperative OCT (iOCT) during pars plana vitrectomy with subretinal tissue plasminogen activator (tPA) injection for subretinal hemorrhage. PATIENTS AND METHODS Eyes that underwent vitrectomy and subretinal injection of tPA were identified from the PIONEER study, a prospective clinical study assessing the feasibility and utility of iOCT in ophthalmic surgery. A microscope-mounted spectral-domain OCT system was utilized for iOCT imaging. Standardized scan protocol and image acquisition were followed for intraoperative imaging. RESULTS iOCT was successfully obtained in four of four eyes. In all cases, increased subretinal fluid was noted, with differential reflectivity visualized between the hemorrhage-tPA interface confirming appropriate localization of tPA injection. Image quality variability was significant. CONCLUSION iOCT can successfully be performed during pars plana vitrectomy with subretinal tPA injection. Utilizing iOCT, appropriate placement of tPA solution and corresponding retinal architectural changes were visualized.

A Novel Segmentation Algorithm for Volumetric Analysis of Macular Hole Boundaries Identified with Optical Coherence Tomography

PURPOSE To demonstrate a novel algorithm for macular hole (MH) segmentation and volumetric analysis. METHODS A computer algorithm was developed for automated MH segmentation in spectral-domain optical coherence tomography (SD-OCT). Algorithm validation was performed by trained graders with performance characterized by absolute accuracy and intraclass correlation coefficient. A retrospective case series of 56 eyes of 55 patients with idiopathic MHs analyzed using the custom algorithm to measure MH volume, base area/diameter, top area/diameter, minimum diameter, and height-to-base diameter ratio. Five eyes were excluded due to poor signal quality (1), motion artifact (1), and failure of surgical closure (3) for a final cohort of 51 eyes. Preoperative MH measurements were correlated with clinical MH stage, baseline, and 6-month postoperative best-corrected Snellen visual acuity (BCVA). RESULTS The algorithm achieved 96% absolute accuracy and an intraclass correlation of 0.994 compared to trained graders. In univariate analysis, MH volume, base area, base diameter, top area, top diameter, minimum diameter, and MH height were significantly correlated to baseline BCVA (P value from 0.0003-0.011). Volume, base area, base diameter, and height-to-base diameter ratio were significantly correlated to 6-month postoperative BCVA (P value from <0.0001-0.029). In multivariate analysis, only base area (P < 0.0001) and volume (P = 0.0028) were significant predictors of 6-month postoperative BCVA. CONCLUSIONS The computerized segmentation algorithm enables rapid volumetric analysis of MH geometry and correlates with baseline and postoperative visual function. Further research is needed to better understand the algorithms role in prognostication and clinical management.

Emerging Therapies for the Treatment of Neovascular Age Related Macular Degeneration

Numerous drugs that show promise in the treatment of neovascular age related macular degeneration are currently being evaluated in early clinical trials. Some of these drugs target the vascular endothelial growth factor pathway while others act on different targets along the angiogenesis cascade. The mechanism of action of these novel therapeutics and the results of early clinical trials will be discussed along with a review of angiogenesis.

Comparison of intravitreal ranibizumab and bevacizumab for the treatment of macular edema secondary to retinal vein occlusion

AIM To compare the efficacy of ranibizumab and bevacizumab for macular edema due to retinal vein occlusion (RVO). METHODS A retrospective study was conducted at a single academic institution. Eighty-one patients naïve to anti-VEGF therapy with RVO and macular edema were identified. Twenty-six eyes were treated with ranibizumab, 33 eyes with bevacizumab, and 22 eyes with bevacizumab then switched to ranibizumab (crossover). The main outcome was change in visual acuity at 3 months, 6 months, and final visit. RESULTS The mean visual acuity improved from 20/80 to 20/40 in the ranibizumab (R) group and from 20/125 to 20/60 in the bevacizumab (B) group (P=0.66). The mean change in central subfield thickness (CST) was -186 and -212µm, respectively (P=0.69). Mean time between injections was 94±21.1d in the R group and 103.8±10.5d in the B group (P=0.78). In the crossover group, mean initial visual acuity was 20/125, reached 20/60 at crossover, and remained 20/60 at conclusion (P=0.91). CONCLUSION Both ranibizumab and bevacizumab are effective for the treatment of RVO and appear to have similar visual and anatomic outcomes. Changing treatments from bevacizumab to ranibizumab did not result in further gains in visual acuity.

Intraoperative OCT Imaging of the Argus II Retinal Prosthesis System

BACKGROUND AND OBJECTIVE Optimal placement of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Sylmar, CA) is critical. Intraoperative optical coherence tomography (OCT) allows for intrasurgical visualization and confirmation of array placement. In this study, two different OCT systems were evaluated to assess the feasibility and utility of this technology during Argus II surgery. PATIENTS AND METHODS Intraoperative OCT was performed on five patients undergoing Argus II implantation at Cole Eye Institute from June 2015 to July 2016. The EnVisu portable OCT (Bioptigen, Morrisville, NC) and microscope-integrated RESCAN 700 (Zeiss, Oberkochen, Germany) intraoperative OCT systems were utilized. The EnVisu was used in three patients and the RESCAN 700 in three of the five patients. Following array tacking, intraoperative OCT was performed over the entire array including the edges and tack. RESULTS Intraoperative OCT allowed for visualization of the array/retina interface. Microscope integration of the OCT system facilitated ease of focusing, real-time feedback, surgeon-directed OCT scanning to the areas of interest, and enhanced image quality at points of interest. CONCLUSIONS Intraoperative imaging of the Argus II electrode array is feasible and provides information about electrode array-retina interface and distance to help guide a surgeon. Microscope integration of OCT appears to provide an optimal and efficient approach to intraoperative OCT during Argus II array placement. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:999-1003.].

Retinal regeneration following OCT-guided laser injury in zebrafish

PURPOSE Establish a focal injury/regeneration model in zebrafish using laser photocoagulation guided by optical coherence tomography (OCT). METHODS Adult zebrafish were imaged by OCT and confocal scanning laser ophthalmoscopy (cSLO) in room air through a contact lens. Using a beam combiner, 532-nm laser photocoagulation was applied using the OCT C-scan image for targeting. Laser spots of 42 to 47 mW were delivered to the retina. At multiple intervals post injury, fish were imaged using both OCT and cSLO to follow the progression of each lesion. Histologic sections and TUNEL staining were performed to monitor the injury response. RESULTS Round lesions (26057 ± 621 μm(2)) localized to the outer retina were successfully applied. Laser application was visualized by real-time OCT and lesions were detectable by both OCT and cSLO in vivo. Lesion size increased 1 day post lesion then decreased in size. Histologic sections showed focal areas of damage localized primarily to the outer retina. By 3 weeks, the damaged areas had regenerated and a fully laminated structure was re-established. However, subtle changes can still be detected by OCT, cSLO imaging, and histology. Infrared darkfield imaging was more sensitive than OCT at revealing subtle changes in regenerated areas. CONCLUSIONS Optical coherence tomography-guided laser photocoagulation is a useful tool for inducing localized lesions and studying retinal regeneration in zebrafish. This novel method will allow us to characterize the cellular and molecular changes that take place at the interface between normal and damaged tissue. Regeneration can be observed using high-resolution OCT and cSLO imaging in vivo.

Retinal and choroidal findings in oxalate retinopathy using EDI-OCT.

A 55-year-old woman with extensive retinal crystalline deposition secondary to primary hyperoxaluria presented with bilateral loss of vision secondary to oxalate retinopathy. Enhanced depth imaging optical coherence tomography revealed intraretinal, subretinal, and intraretinal and subretinal pigment epithelium, and choroidal focal hyperreflective structures consistent with both neurosensory and uveal deposition of oxalate crystals. Serial optical coherence tomography revealed continued crystalline deposition with progressive retinal atrophy.

Comparison of anti-VEGF therapies on fibrovascular pigment epithelial detachments in age-related macular degeneration

Background The aim is to compare the therapeutic effects of three antivascular endothelial growth factor (VEGF) drugs (bevacizumab, aflibercept and ranibizumab) on fibrovascular pigment epithelial detachments (fvPEDs) in age-related macular degeneration (AMD). Methods This was a retrospective, comparative, consecutive case series of 88 unique eyes with fvPEDs in neovascular AMD treated with anti-VEGF monotherapy for a minimum of 6 months. All eyes were treatment naive. Diagnosis was confirmed retrospectively by fluorescein angiography and spectral-domain optical coherence tomography. Exclusion criteria included serous/drusenoid PEDs or patients who switched anti-VEGF. Mean follow-up across all therapies was 313.9±85.3 days. Results Average age of all patients was 80.6 years. Baseline maximum subfoveal PED height was 326.8±185.1 μm, 394.5±238.6 μm and 258.0±145.3 μm for bevacizumab, aflibercept and ranibizumab, respectively (p=0.05). All patients had subretinal fluid, intraretinal fluid or a combination of the two at an initial presentation. Central retinal thickness decreased at all time points compared with baseline across all three anti-VEGF therapies. Subfoveal PED height decreased in patients treated with aflibercept at all time points and decreased in patients treated with bevacizumab at 1-month, 3-month and 6-month time points. Aflibercept reduced PED height more than bevacizumab at 1-month and 12-month follow-ups (p=0.02 and p=0.03, respectively) and ranibizumab at 1-month and 6-month follow-ups (p=0.03 and p=0.02, respectively). No differences in best-corrected visual acuity were appreciated at any time point between drugs. Conclusions There was a significant reduction in subfoveal PED height for aflibercept and bevacizumab compared with baseline. A direct comparison of drugs demonstrated a beneficial reduction of PED height, albeit inconsistently, favouring aflibercept. There were no differences in visual acuity across the groups at any time point.

Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice

Aim To determine the impact of initial visual acuity (VA) on anti-vascular endothelial growth factor (VEGF) treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice. Methods A retrospective study was conducted at a single academic institution to identify 177 treatment naïve patients with macular oedema secondary to branch retinal vein occlusion (BRVO), hemiretinal vein occlusion (HRVO) and central retinal vein occlusion (CRVO) treated with intravitreal anti-VEGFs. Exclusion criteria included prior intravitreal injection or presence of active confounding ocular disease. Patients were stratified by initial VA; main outcomes measured were average change in VA and mean absolute change in central subfield thickness (CST) at 6 and 12 months. Results Patients with BRVO with initial VA of 20/40 or better had no significant changes in average letters gained and CST from baseline (+2.6 letters, p=0.42; −48.94 µm, p=0.12) compared with patients with initial VA between 20/50 and 20/300 (+13.2 letters, p<0.001; −98.20 µm, p<0.001) after 12 months. Patients with CRVO/HRVO with initial VA of 20/320 or worse had the most improvement in average letters gained and CST from baseline (+42.2 letters, p<0.001; −182.84 µm, p=0.004) with anti-VEGF therapy compared with patients with initial VA between 20/50 and 20/300 (+9.4 letters, p=0.016; −160.87 µm, p<0.001) and patients with initial VA of 20/40 or better (−9.6 letters, p=0.14; −47.92 µm, p=0.38). Conclusions For macular oedema secondary to retinal vein occlusion, anti-VEGF treatment can result in a greater improvement in average letters gained and in CST for those with poor initial VA compared with those with better initial VA.