Sarah Mrejen

Optical coherence tomography: imaging of the choroid and beyond.

Seventy percent of the blood flow to the eye goes to the choroid, a structure that is vitally important to the function of the retina. The in vivo structure of the choroid in health and disease is incompletely visualized with traditional imaging modalities, including indocyanine green angiography, ultrasonography, and spectral domain optical coherence tomography (OCT). Use of new OCT modalities, including enhanced depth imaging OCT, image averaging, and swept-source OCT, have led to increased visualization of the choroidal anatomy. The correlation of these new anatomical findings with other imaging modalities results increases understanding of many eye diseases and recognises of new ones. The status of the choroid appears to be a crucial determinant in the pathogenesis of diseases such as age-related choroidal atrophy, myopic chorioretinal atrophy, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. Extension of these imaging techniques has provided insights into abnormalities of the sclera and optic nerve. Future developments will include blood flow information, 3D rendering of various ocular structures, and the ability to evaluate changes in 3D structural information over time (4D imaging).

Visual and anatomical outcomes of intravitreal aflibercept in eyes with persistent subfoveal fluid despite previous treatments with ranibizumab in patients with neovascular age-related macular degeneration.

Purpose: To assess the efficacy of intravitreal aflibercept (2.0 mg) in patients with treatment-resistant neovascular age-related macular degeneration. Methods: Retrospective analysis of eyes treated with aflibercept with persistent subretinal and/or intraretinal fluid despite previous treatments with intravitreal ranibizumab (0.5 mg). All patients were switched to intravitreal aflibercept (2.0 mg) and analyzed after 3 consecutive injections and after 6 months of treatment. Main outcome measures included change in visual acuity, central foveal thickness, and the height and diameter of the pigment epithelial detachment on the subfoveal scan on optical coherence tomography. Results: Thirty-four eyes of 33 patients were analyzed. Mean duration of symptoms and average number of previous injections with anti–vascular endothelial growth factor agents was 44.7 ± 29.8 months (interquartile range [IQR] 24–76 months) and 28.6 ± 20.1 (IQR 10–47), respectively. At the 6-month follow-up, mean visual acuity and central foveal thickness improved significantly from 20/75 (logarithm of minimum angle of resolution 0.57 ± 0.36; IQR 0.30–1.0) and 416 ± 217 &mgr;m (IQR 263–487 &mgr;m) at baseline to 20/60 (logarithm of minimum angle of resolution 0.47 ± 0.32; IQR 0.30–0.60) (P = 0.004) and 248 ± 171 &mgr;m (IQR 235–419 &mgr;m) (P < 0.001), respectively. Maximum pigment epithelial detachment height improved significantly from 260 ± 162 &mgr;m (IQR 129–368 &mgr;m) to 214 ± 142 &mgr;m (IQR 111–305 &mgr;m) (P < 0.001) and PED diameter decreased significantly from 3,265 ± 1,622 &mgr;m (IQR 2,353–4,555 &mgr;m) to 2,949 ± 1,653 &mgr;m (IQR 1,721–4,484 &mgr;m) (P = 0.04). Conclusion: Intravitreal injections of aflibercept resulted in a significant improvement in visual and anatomical outcomes in eyes with persistent subfoveal fluid despite previous treatment with ranibizumab.

Assessing the Cone Photoreceptor Mosaic in Eyes with Pseudodrusen and Soft Drusen In Vivo Using Adaptive Optics Imaging

PURPOSE To investigate the cone photoreceptor mosaic in eyes with pseudodrusen as evidenced by the presence of subretinal drusenoid deposits (SDD) and conventional drusen using adaptive optics (AO) imaging integrated into a multimodal imaging approach. DESIGN Observational case series. PARTICIPANTS Eleven patients (11 eyes) with pseudodrusen and 6 patients (11 eyes) with conventional drusen. METHODS Consecutive patients were examined using near-infrared reflectance (IR) confocal scanning laser ophthalmoscopy (SLO) and eye-tracked spectral-domain optical coherence tomography (SD-OCT) and flood-illuminated retinal AO camera of nonconfluent pseudodrusen or conventional drusen. Correlations were made between the IR-SLO, SD-OCT, and AO images. Cone density analysis was performed on AO images within 50 × 50-μm windows in 5 regions of interest overlying and in 5 located between SDD or conventional drusen with the same retinal eccentricity. MAIN OUTCOME MEASURES Cone densities in the regions of interest. RESULTS The pseudodrusen correlated with subretinal accumulations of material in SD-OCT imaging and this was confirmed in the AO images. Defects in the overlying ellipsoid zone band as seen by SD-OCT were associated with SDD but not conventional drusen. The mean ± standard deviation cone density was 8964 ± 2793 cones/mm(2) between the SDD and 863 ± 388 cones/mm² over the SDD, a 90.4% numerical reduction. By comparison the mean cone packing density was 9838 ± 3723 cones/mm² on conventional drusen and 12,595 ± 3323) cones/mm² between them, a 21.9% numerical reduction. The difference in cone density reduction between the two lesion types was highly significant (P <0.001). CONCLUSIONS The pseudodrusen in these eyes correlated with subretinal deposition of material in multiple imaging modalities. Reduced visibility of cones overlying SDD in the AO images can be because of several possible causes, including a change in their orientation, an alteration of their cellular architecture, or absence of the cones themselves. All of these explanations imply that decreased cone photoreceptor function is possible, suggesting that eyes with pseudodrusen appearance may experience decreased retinal function in age-related macular degeneration independent of choroidal neovascularization or retinal pigment epithelial atrophy.

Multimodal Imaging of Optic Disc Drusen

PURPOSE To evaluate optic disc drusen, extracellular protein deposits known to contain numerous aggregates of mitochondria, using multimodal modalities featuring optical coherence tomography (OCT) and autofluorescence imaging. DESIGN Retrospective observational case series. METHODS Eyes with optic nerve drusen were examined with enhanced depth imaging (EDI)-OCT, swept source OCT, and fundus autofluorescence using a fundus camera. RESULTS Twenty-six eyes of 15 patients with optic disc drusen were evaluated. EDI-OCT and swept source OCT showed multiple optic disc drusen at different levels; most were located immediately anterior to the lamina cribrosa. The drusen were ovoid regions of lower reflectivity that were bordered by hyperreflective material, and in 12 eyes (46.2%) there were internal hyperreflective foci. The mean diameter of the optic disc drusen as measured in OCT images was 686.8 (standard deviation ± 395.2) μm. There was a significant negative correlation between the diameter of the optic disc drusen and the global retinal nerve fiber layer thickness (r = -0.61, P = .001). There was a significant negative correlation between proportion of the optic disc drusen area occupied by optic nerve drusen as detected by autofluorescence imaging and the global retinal nerve fiber layer thickness (r = -0.63, P = .001). CONCLUSIONS Deeper-penetration OCT imaging demonstrated the internal characteristics of optic disc drusen and their relationship with the lamina cribrosa in vivo. This study also showed that both the larger the drusen and the more area of the optic canal occupied by drusen, the greater the associated retinal nerve fiber layer abnormalities.

Multimodal Imaging Of Pigment Epithelial Detachment: A Guide to Evaluation

Purpose: To describe the spectrum of pigment epithelial detachments (PEDs) occurring mainly in age-related macular degeneration and central serous chorioretinopathy and also in other inflammatory, neoplastic and iatrogenic, retinal, and systemic disorders. Methods: Pigment epithelial detachments are divided into drusenoid, serous, vascularized, or mixed categories. Results: The clinical presentation, classification, and natural history of PEDs are reviewed as illustrated with multimodal imaging combining traditional and novel imaging techniques, including fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and spectral domain optical coherence tomography. Most PEDs occur because of pathophysiologic mechanisms taking place below the retinal pigment epithelium that are difficult to identify with conventional imaging modalities. Enhanced depth imaging optical coherence tomography and indocyanine green angiography allow a better analysis of the subretinal pigment epithelium compartment. Conclusion: The differentiation between various kinds of PEDs is essential because each PED type is a distinct entity that has a specific pathogenesis, natural history, prognosis, and optimal treatment strategy.

Subretinal hyperreflective exudation associated with neovascular age-related macular degeneration.

Purpose: To describe the multimodal imaging findings of subretinal hyperreflective exudation (SHE) observed in association with choroidal neovascularization and to distinguish SHE from other forms of subretinal hyperreflective material (SHM) seen in patients with age-related macular degeneration and other macular disorders. Methods: A retrospective study on 46 eyes of 42 patients with SHE associated with Types 1, 2, and 3 choroidal neovascularization secondary to neovascular age-related macular degeneration. Patients were examined using multimodal imaging, including color photography, near-infrared reflectance imaging, spectral domain optical coherence tomography, fluorescein angiography, fundus autofluorescence imaging, and indocyanine green angiography. Clinical and imaging characteristics were evaluated at baseline, after the initiation of intravitreal antivascular endothelial growth factor therapy, and during the resolution of SHE. Results: Forty-five of the 46 eyes were treatment naive. The mean ± SD age at the first detection of SHE was 77.2 ± 10.1 years. The mean ± SD follow-up was 2.1 ± 0.6 years. Fluorescein angiography was performed in 42 eyes and demonstrated leakage and/or staining of underlying or adjacent choroidal neovascularization but not of the SHE itself in all eyes. On fluorescein angiography, SHE was transparent in 29 eyes and blocking in 7 eyes. In 32 eyes, SHE showed isoautofluorescence on fundus autofluorescence imaging, and in 8 eyes, SHE showed varying degrees of hyperautofluorescence. Indocyanine green angiography was performed in eight eyes and demonstrated hyperfluorescence of SHE in seven eyes. In eight eyes, SHE was the only evidence of neovascular activity. All eyes having follow-up (42 eyes) showed resolution of the subretinal material with partial or full reconstitution of the ellipsoid zone after a median of 2 injections range (1–16 injections). Subretinal hyperreflective exudation persisted for a median of 9 weeks (range, 4–60 weeks) after the initiation of treatment. The mean visual acuity before treatment was 0.619 (20/83), and it improved to 0.380 (20/48) (P = 0.03) after the resolution of SHE. Conclusion: Subretinal hyperreflective exudation differs from other types of SHM based on the findings from multimodal imaging. This novel type of SHM likely represents a sign of active neovascular age-related macular degeneration distinct from subretinal fluid, hemorrhage, neovascular tissue, lipid, pigment hyperplasia, subretinal fibrosis, and the SHM observed with acquired vitelliform lesions. Intravitreal antivascular endothelial growth factor agents can be used to successfully resolve SHE, often resulting in better visual outcomes in eyes manifesting this form of exudation.

Acute Zonal Occult Outer Retinopathy: A Classification Based on Multimodal Imaging

IMPORTANCE We describe the multimodal imaging in a group of patients showing a distinct clinical entity that best represents acute zonal occult outer retinopathy (AZOOR). OBJECTIVE To propose a classification of AZOOR based on clinical fundus and multimodal imaging. DESIGN, SETTING AND PARTICIPANTS A retrospective review of patients diagnosed as having AZOOR at 2 centers. After reviewing more than 400 cases diagnosed or referred to us as AZOOR or AZOOR complex, we assembled 30 cases that fit our current definition; (48 eyes) with a median age at diagnosis of 47 years (age range, 17-86 years) and a mean follow-up period of 39 months. Twenty patients were female. Eighteen patients had initially been seen with bilateral lesions, mostly asymmetric (4 cases were symmetric). Most patients had no remarkable medical or ocular history. The median visual acuity at the time of presentation was 20/25 (range, 20/20 to 20/400). MAIN OUTCOMES AND MEASURES Multimodal imaging, including fundus photography, fluorescein and indocyanine green angiography, fundus autofluorescence imaging, and corresponding eye-tracked spectral-domain coherence tomography imaging. RESULTS Each patient was initially seen with visual symptoms of photopsia and scotoma, and most had a detectable lesion in the fundus evident clinically or detected on multimodal imaging. The clinical appearance of the AZOOR lesions varied depending on their duration and location, but some features were characteristic, including a demarcating line of the progression at the level of the outer retina and a trizonal pattern of sequential involvement of the outer retina, retinal pigment epithelium, and choroid, as well as frequent zonal progression. Advanced cases of AZOOR demonstrated disruption of the inner and outer retina and severe damage or loss of the retinal pigment epithelium and the choroid. CONCLUSIONS AND RELEVANCE A specific definition of AZOOR based on multimodal imaging is proposed to help physicians distinguish it from other diseases of the posterior fundus, including white spot syndromes and autoimmune, hereditary, paraneoplastic, toxic, and other inflammatory retinopathies.

Retinal Pigment Epithelial Cell Loss Assessed by Fundus Autofluorescence Imaging in Neovascular Age-related Macular Degeneration

PURPOSE To characterize retinal pigment epithelial (RPE) cell loss as evidenced by autofluorescence imaging in patients with neovascular age-related macular degeneration (AMD). DESIGN Retrospective cohort study. PARTICIPANTS There were 162 eyes of 116 consecutive patients with neovascular AMD examined in a retinal practice. METHODS Each patient underwent a complete examination including autofluorescence imaging. Areas of confluent absence of autofluorescence signal of at least 0.5 mm in greatest linear diameter were measured within the macular area. Patient demographic and examination data were evaluated in relation to the autofluorescence data. MAIN OUTCOME MEASURES Prevalence and progression of confluent areas of absent autofluorescence and the relationship these areas had with visual acuity. RESULTS The mean age of the patients was 82.9 years, and the mean visual acuity was 20/71 (logarithm minimum angle of resolution [logMAR], 0.55). Confluent loss of autofluorescence was seen in 58.6% of eyes at baseline, and the median area of absent autofluorescence among those was 1.57 mm(2) (interquartile range [IQR], 0.62-4.32 mm(2)). Using generalized estimation equation modeling, the significant predictors for area of confluent absent autofluorescence at baseline were duration of disease and any previous treatment with photodynamic therapy. The significant predictor of baseline visual acuity was baseline area of confluent absent autofluorescence. Follow-up was available for 124 (76.5%) eyes, with a mean follow-up of 2.9 years. By then, the mean visual acuity was 20/90 (logMAR, 0.65), and 79% of eyes had confluent areas of absent autofluorescence, the large majority of which affected the central macula. The median area of absent autofluorescence was 3.61 mm(2) (IQR, 1.16-7.11 mm(2)). The best predictor of final visual acuity was the area of absent autofluorescence at the final follow-up. CONCLUSIONS Confluent absence of autofluorescence, a measure signifying RPE loss, was a significant predictor of visual acuity both at baseline and at final follow-up. This is the first study to document the prevalence, rate of progression, and factors associated with measures of confluent RPE loss in patients with neovascular AMD. Application of strategies to limit RPE cell loss may prove useful in eyes with neovascular AMD.

Management of retinal detachment in Coats disease. Study of 15 cases.

Purpose: To correlate the final outcome with the initial presentation and treatment in Coats disease retinal detachment. Methods: The records of 15 patients with retinal detachment were evaluated retrospectively regarding the age at the time of diagnosis, initial presentation, methods of treatment, visual and anatomic results, and complications. Changes in vision and retinal status were noted and correlated with the different methods of treatment to propose a therapeutic strategy. Results: In 15 patients (15 eyes), with a mean follow-up of 28 months (range, 6 months to 7 years), Coats disease was diagnosed at a mean age of 3.4 years (range 3 months to 15 years). Primary management was laser photocoagulation in seven patients, cryotherapy in two, and vitreoretinal surgery in six. Additional treatment was necessary in nine patients of whom six had laser photocoagulation, one had cryotherapy, and two had vitreoretinal surgery. Visual stability was achieved in 12 cases. Anatomic improvement was achieved in 12 eyes (3 cases of phthisis bulbi). No enucleation was ultimately necessary. Conclusions: Carefully selected treatment can improve almost each eye with Coats disease complicated by retinal detachment. Although visual outcome is poor, anatomic improvement or stability is the main goal of the management.

The Relationship Between Pseudodrusen And Choroidal Thickness

Purpose: To determine the relationship between pseudodrusen as evidenced by the presence of subretinal drusenoid deposits and choroidal thickness using a multimodal imaging approach. Methods: Two sets of data were analyzed. The first set was composed of consecutive patients older than 60 years with either high myopia or pseudodrusen. Correlations were calculated between the subfoveal choroidal thickness and the presence of pseudodrusen. The second set of data was obtained from a previously published data examining 90 consecutive eyes with nonexudative age-related macular degeneration so that the relationship between pseudodrusen and subfoveal choroidal thickness could be analyzed. Results: There were 96 eyes of 53 patients in the first data set, 36 (67.9%) were female and 17 (32.1%) were male. There were 34 patients (61 eyes) in the High Myopia group and 19 patients (35 eyes) in the Primary Pseudodrusen group. The mean age of the Primary Pseudodrusen group was 83.7 years and that of the High Myopia group was 74.9 years, a difference that was significant (P < 0.001). Of the 61 eyes in the High Myopia group, only 3 (4.9%) had pseudodrusen and 0 had conventional drusen. In the Primary Pseudodrusen group, all had pseudodrusen by definition, but 28 (80%) also had conventional drusen. The mean subfoveal choroidal thickness was 181.7 &mgr;m (median, 147; interquartile range, 65–225 &mgr;m) in the Primary Pseudodrusen group and 59 &mgr;m (median, 36; interquartile range, 21–90 &mgr;m) in the myopic group. Generalized estimating equation analysis showed that eyes with pseudodrusen had thicker subfoveal choroidal thickness than eyes without, a result driven by the High Myopia group. In the second set of data, while the absolute number of eyes with pseudodrusen had a choroidal thickness between 201 &mgr;m and 250 &mgr;m, the proportion with pseudodrusen was higher in eyes with thinner choroids, with a broad peak between 50 &mgr;m and 100 &mgr;m. Conclusion: Our results are not consistent with a simple cause or consequence relationship between pseudodrusen and choroidal thinning, but rather with a third yet unknown factor impacting both the pseudodrusen appearance and the choroidal thinning in susceptible populations. The reasons for the relative lack of drusen and pseudodrusen formation in high myopes need to be ascertained.