Sharif El-Emam

Choroidal Volume Variations with Age, Axial Length, and Sex in Healthy Subjects: A Three-Dimensional Analysis

PURPOSE To demonstrate the 3-dimensional choroidal volume distribution in healthy subjects using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with age, sex, and axial length. DESIGN Retrospective case series. PARTICIPANTS A total of 176 eyes from 114 subjects with no retinal or choroidal disease. METHODS The EDI SD-OCT imaging studies of healthy patients who had undergone a 31-raster scanning protocol on a commercial SD-OCT device were reviewed. Manual segmentation of the choroid was performed by 2 retinal specialists. A macular choroidal volume map and 3-dimensional topography were automatically created by the built-in software of the device. Mean choroidal volume was calculated for each Early Treatment Diabetic Retinopathy Study (ETDRS) subfield. Regression analyses were used to evaluate the correlation between macular choroidal volume and age, sex, and axial length. MAIN OUTCOME MEASURES Three-dimensional topography and ETDRS-style volume map of the choroid. RESULTS Three-dimensional topography of the choroid and volume map was obtained in all cases. The mean choroidal volume was 0.228 ± 0.077 mm(3) for the center ring and 7.374 ± 2.181 mm(3) for the total ETDRS grid. The nasal quadrant showed the lowest choroidal volume, and the superior quadrant showed the highest choroidal volume. The temporal and inferior quadrants did not show different choroidal volume values. Choroidal volume in all the EDTRS rings was significantly correlated with axial length after adjustment for age (P < 0.0001), age after adjustment for axial length (P < 0.0001), and sex after adjustment for axial length (P < 0.05). Choroidal volume decreases by 0.54 mm(3) (7.32%) for every decade and by 0.56 mm(3) (7.59%) for every millimeter of axial length. Male subjects have a 7.37% greater choroidal volume compared with that of female subjects. CONCLUSIONS Enhanced depth imaging SD-OCT is a noninvasive and well-tolerated procedure with an excellent ability to visualize 3-dimensional topography of the choroid and to measure choroidal volume at the posterior pole using manual segmentation. Age and axial length are inversely correlated with choroidal volume, most likely leading to changes in retinal metabolic support in elderly, highly myopic patients. Sexual differences should be considered when interpreting an EDI SD-OCT scan of the choroid. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Repeatability and Reproducibility of Manual Choroidal Volume Measurements Using Enhanced Depth Imaging Optical Coherence Tomography

PURPOSE To evaluate the repeatability and reproducibility of manual choroidal volume (CV) measurements by spectral domain- optical coherence tomography (SD-OCT) using enhanced depth imaging (EDI). METHODS Sixty eyes of 32 patients with or without any ocular chorioretinal diseases were enrolled prospectively. Thirty-one choroidal scans were performed on each eye, centered at the fovea, using a raster protocol. Two masked observers demarcated choroidal boundaries by using built-in automated retinal segmentation software on two separate sessions. Observers were masked to each others and their own previous readings. A standardized grid centered on the fovea was positioned automatically by OCT software, and values for average CVs and total CVs in three concentric rings were noted. The agreement between the intraobserver measurements or interobserver measurements was assessed using the concordance correlation coefficient (CCC). Bland-Altman plots were used to assess the clinically relevant magnitude of differences between inter- and intraobserver measurements. RESULTS The interobserver CCC for the overall average CV was very high, 0.9956 (95% confidence interval [CI], 0.991-0.9968). CCCs for all three Early Treatment Diabetic Retinopathy Study concentric rings between two graders was 0.98 to 0.99 (95% CI, 0.97-0.98). Similarly intraobserver repeatability of two graders also ranged from 0.98 to 0.99. The interobserver coefficient of reproducibility was approximately 0.42 (95% CI, 0.34-0.5 mm(3)) for the average CV. CONCLUSIONS CV measurement by manual segmentation using built-in automated retinal segmentation software on EDI-SD-OCT is highly reproducible and repeatable and has a very small range of variability.

Characterization of Microaneurysm Closure After Focal Laser Photocoagulation in Diabetic Macular Edema

PURPOSE To characterize microaneurysm closure following focal laser photocoagulation in diabetic macular edema (DME) using simultaneous fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). DESIGN Retrospective observational case series. METHODS Leaking microaneurysms (n = 123) were analyzed in eyes (n = 29) with nonproliferative diabetic retinopathy (NPDR) that underwent navigated focal laser photocoagulation in DME and were followed at 3, 6, and 12 months. Closure of diabetic microaneurysms was characterized in detail following focal laser using SD-OCT. RESULTS Closure rate of microaneurysms by both FA and SD-OCT was 69.9% (84/123), 79.7% (98/123), and 82.9% (102/123) at 3, 6, and 12 months, respectively. Microaneurysm closure rate increased at 6 and 12 months compared to 3 months (P < .003, P < .001). Over half of closed microaneurysms (45/86, 52.3%) left hyperreflective spots while the remaining half (41/86, 47.7%) disappeared without any hyperreflectivity by SD-OCT at 3 months. Hyperreflective spots decreased at 6 (36/99, 36.4%) and 12 months (17/102, 16.7%) with a concomitant increase in complete loss of reflectivity at 6 (63/99, 63.6%) and 12 months (85/102, 83.3%). Smaller outer and inner diameters and heterogeneous lumen reflectivity were positively associated with microaneurysm closure at 12 months (P < .0001, P < .001, P < .03). CONCLUSIONS Characterization of microaneurysms following focal laser photocoagulation resulted in hyperreflective spots and complete resolution of all reflectivity using SD-OCT. Smaller microaneurysms and those with heterogeneous lumen were positively associated with microaneurysm closure. These findings provide greater understanding of localized retinal changes following focal laser photocoagulation in DME treatment.

A degenerative retinal process in HIV-associated non-infectious retinopathy

HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner–retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients.

A novel navigated laser system brings new efficacy to the treatment of retinovascular disorders

The laser photocoagulation is now treatment of choice for various retinovascular disorders. Conventional slit-lamp based laser delivery systems have many limitations including, questionable accuracy, need of contact lens with local anesthesia, and inadvertent damage to fovea. Navigated laser system, a fundus camera based laser delivery system with computer based laser planning and laser treatment without contact lens achieves improved patient compliance, improved accuracy, and treatment ease for the physician, efficient panretinal photocoagulation pattern laser, excellent documentation, and advanced laser training. This article compares navigated laser systems with available conventional and PASCAL laser systems based on the literature and personal experience of the authors.

Macular choroidal volume variations in highly myopic eyes with myopic traction maculopathy and choroidal neovascularization.

Purpose: To compare the choroidal volume (CV) between emmetropic and highly myopic eyes, and to assess if the presence of myopic fundus abnormalities, myopic traction maculopathy, or choroidal neovascularization affects the CV. Methods: We retrospectively reviewed imaging studies of 98 eyes of 98 patients who underwent CV measurement on optical coherence tomography. We included 31 emmetropic eyes (Group 1), 36 highly myopic eyes without vitreoretinal or choroidal pathologies (Group 2), 21 highly myopic eyes with traction maculopathy (Group 3), and 10 highly myopic eyes with history of choroidal neovascularization (Group 3). Eyes with chorioretinal atrophy were excluded. Regression analysis was performed to evaluate the correlation between CV and multiple variables. Results: Choroidal volume was lower in Group 2 than in Group 1 (P < 0.001), and in Groups 3 and 4 than in Group 2 (P < 0.001 and P = 0.002, respectively). Age (P = 0.002), axial length (P < 0.001), sex (P = 0.047), staphyloma (P < 0.001), and myopic group (P = 0.05) were independent predictors for the final CV (R2 = 0.645). In highly myopic eyes, CV decreased by 0.32 mm3 for every 10 years and by 0.49 mm3 per millimeter of axial length. Conclusion: Choroidal thinning is present in highly myopic eyes compared with emmetropic eyes, and is related to age, axial length, sex, and staphyloma. However, myopic eyes with coexisting myopic traction maculopathy or history of choroidal neovascularization have more severe thinning, likely leading to insufficient metabolic supplementation for the macula.

Correlation of spectral domain optical coherence tomography characteristics with visual acuity in eyes with subfoveal scarring after treatment for wet age-related macular degeneration

Purpose: Correlating spectral domain optical coherence tomography characteristics with final best-corrected visual acuity (BCVA) in eyes with subfoveal scarring after treatment for wet age-related macular degeneration. Methods: Seventy-nine eyes from 64 subjects, who developed subfoveal scarring after treatment of wet age-related macular degeneration, were retrospectively studied. Spectral domain optical coherence tomography characteristics were analyzed, including percentage disruption of inner segment/outer segment junction and external limiting membrane, central macular thickness, subfoveal scar thickness, subretinal scar area, and proximity of retina with intact outer structures to the fovea. A multivariate stepwise regression analysis was performed with the final BCVA logarithm of minimum angle of resolution as a response and the above-identified spectral domain optical coherence tomography variables as predictors. Results: There was no correlation between the final BCVA and any of the demographic data, treatment modality received, and central macular thickness. The final BCVA was significantly correlated with the percentage of inner segment/outer segment disruption (P = 0.011), external limiting membrane disruption (P = 0.005), and scar area on spectral domain optical coherence tomography (P = 0.018). Multivariate analysis showed that the baseline BCVA and distance between the fovea and nearest retina with intact outer structures are the most predictive of the final BCVA (R2 = 0.52). Conclusion: Baseline BCVA and integrity of outer retinal structures are good predictors of the final BCVA of wet age-related macular degeneration patients developing scarring after treatment.

Fluorescein angiography versus optical coherence tomography-guided planning for macular laser photocoagulation in diabetic macular edema.

Purpose: To compare laser photocoagulation plans for diabetic macular edema (DME) using fluorescein angiography (FA) versus optical coherence tomography (OCT) thickness map superimposed on the retina. Methods: Fourteen eyes with DME undergoing navigated laser photocoagulation with navigated photocoagulator had FA taken using the same instrument. Optical coherence tomography central retinal thickness map was imported to the photocoagulator and with same magnification aligned onto the retina. Three retina specialists placed laser spot marks separately on FA and OCT image in a masked fashion. The spots placed by each physician were compared between FA and OCT and among physicians. The area of dye leakage on FA and increased central retinal thickness on OCT of the same eye were also compared. Results: The average number of spots using FA and OCT template was 36.64 and 40.61, respectively (P = 0.0201). The average area of dye leakage was 7.45 mm2, whereas the average area of increased central retinal thickness on OCT of the same eye was 10.92 mm2 (P = 0.013). Conclusion: There is variability in the treatment planning for macular photocoagulation with a tendency to place more spots when guided by OCT than by FA. Integration of OCT map aligned to the retina may have an impact on treatment plan once such information is available.

Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis

Purpose To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Methods Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Results Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308–6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Conclusion Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

Significance of the hyperautofluorescent ring associated with choroidal neovascularisation in eyes undergoing anti-VEGF therapy for wet age-related macular degeneration.

Aim To characterise the presence of a hyperautofluorescent (HAF) ring associated with choroidal neovascularisation (CNV) complex in patients with wet age-related macular degeneration (AMD). Methods Fundus autofluorescence images and spectral-domain optical coherence tomography (OCT) scans from 362 eyes with wet AMD were reviewed. The presence and size of an HAF ring associated with the CNV complex was evaluated. A subgroup of 64 treatment-naive eyes with new-onset CNV was studied to analyse the relationship between pretreatment OCT characteristics and the presence of the HAF ring. Results An HAF ring was present in 38% of the entire cohort of eyes and in 39% of treatment-naive eyes. The presence of the HAF ring was significantly correlated with the extent of baseline subretinal fluid (SRF) on OCT (p=0.0113), the number of antivascular endothelial growth factor (VEGF) injections (p=0.0439) and the number of treatment cycles (p=0.0154). Eyes with an HAF ring were more likely to have disruption of the ellipsoid zone line once the SRF was resolved compared with eyes without an HAF ring (p=0.0002). In multivariate analysis, the best predictors for HAF ring were the baseline area of SRF (p=0.0449) and the number of anti-VEGF treatments received (p=0.0568). Conclusions Nearly 40% of wet AMD eyes had an HAF ring. In treatment-naive eyes, the HAF ring had a significant association with SRF and was found as early as the baseline measurement and as long as 18 months after beginning treatment, persisting for up to 6 years after the initial diagnosis. Its association with baseline SRF and disruption of the ellipsoid zone line of the photoreceptors on OCT could indicate continuous stress on the outer retinal structures after exposure to prolonged SRF and/or transmitted autofluorescence from loss of the photoreceptors overlying the retinal pigment epithelium.