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We report a case of an uncommon presentation of Epstein-Barr virus (EBV)-associated plasma cell neoplasm in a patient with a history of prostate cancer and hairy cell leukemia (HCL) in remission after chemotherapy. The diagnosis of an EBV-associated plasma cell neoplasm was challenging as initially the findings were also compatible with a recurrence of HCL. We highlight the value of diagnostic vitrectomy to achieve the diagnosis. Our particular case demonstrates the importance of diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of an unknown cause to confirm the diagnosis.

Introduction Uveal melanoma is most commonly treated with radiotherapy, destroying the tumour cells with adequate safety margins and limiting collateral damage to surrounding structures to preserve maximal vision. We used optical coherence tomography (OCT) to study the effects of radiotherapy on the retina. Methods Patients with posteriorly located choroidal melanoma treated with proton beam radiotherapy (PBR) and ruthenium-106 brachytherapy between January 2010 and June 2014 underwent spectral domain OCT. Results Images of 32 patients following ruthenium-106 brachytherapy and 44 patients following proton beam teletherapy were analysed. Following plaque brachytherapy, an early marked disruption of the outer retinal layers could be observed in 30 cases (94%) with retinal atrophy evident in 26 cases (81%). In contrast, the images from patients who underwent PBR showed subtle outer retinal layer change with 16 cases (36%) showing some inner-outer segment junction disruption by 6 months and 63% by 24 months with minimal atrophy. In cases with tumours Conclusion In comparison to ruthenium-106 plaque brachytherapy, PBR leads to more subtle and slower changes in the outer retinal layers enabling retention of visual function for longer. The difference in dosing regime and dose distribution across the tumour is likely to be causative for this structural differential.

PURPOSE To evaluate retinal vessel diameters in relation to different severity grades of diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT). METHODS Patients with varying degrees of nonproliferative DR (NPDR) underwent circular OCT scans centered on the optic nerve head using a SD-OCT. These cases were retrospectively reviewed. The presence and severity of DR was assessed using Early Treatment Diabetic Retinopathy Study protocols. The 5 largest retinal arterioles and venules were labeled and measured on OCT scans for each patient according to previously published methods. Vertical vessel inner contour diameter, vertical vessel outer contour diameter, and reflectance shadowing width were among the documented parameters. RESULTS Of 59 eyes from 45 patients examined, 30 (50.2%) and 29 (49.8%) had mild and severe NPDR, respectively. Eyes with severe NPDR had narrower mean arteriolar vertical vessel inner diameter (87.9 ± 10.8 μm), vertical vessel outer diameter (119.1 ± 9.7 μm), and vessel shadow width (78.8 ± 10.9 μm) than eyes with mild NPDR (89.8 ± 12.1 μm, 120.9 ± 12.9 μm, 81.3 ± 15.3 μm). However, the differences were not statistically significant (p = 0.53, 0.55, 0.47). No correlation was shown between the severity of NPDR and arteriolar parameters (p = 0.31, 0.59, 0.75). Wider venular diameters were associated with increasing severity of NPDR (p

To describe a spectral domain optical coherence (OCT)-assisted method of measuring retinal vessel diameters.All Patients with an OCT circle scan centered at the optic nerve head using a Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were retrospectively reviewed. Individual retinal vessels were identified on infrared reflectance (IR) images and given unique labels both on IR and spectral domain OCT (SD-OCT). Vessel width and vessel types obtained by IR were documented as ground truth. From OCT, measurements of each vessel, including horizontal vessel contour diameter, vertical vessel contour diameter, horizontal hyperreflective core diameter, and reflectance shadowing width, were assessed.A total of 220 vessels from 13 eyes of 12 patients were labeled, among which, 194 vessels (88 arteries and 65 veins confirmed from IR) larger than 40 microns were included in the study. The mean vessel width obtained from IR was 107.9 ± 36.1 microns. A mean vertical vessel contour diameter of 119.6 ± 29.9 microns and a mean horizontal vessel contour diameter of 124.1 ± 31.1 microns were measured by SD-OCT. Vertical vessel contour diameter did not differ from vessel width in all subgroup analysis. Horizontal vessel contour diameter was not significantly different from vessel width for arteries and had strong or very strong correlation with vessel width for veins.In our study, vertical vessel contour diameter measured by current commercially available SD-OCT was consistent with vessel width obtained by IR with good reproducibility. This SD-OCT based method could potentially be used as a standard measurement procedure to evaluate retinal vessel diameters and their changes in ocular and systemic disorders.

To describe the treatment response to aflibercept in patients with exudative age-related macular degeneration that showed insufficient or diminishing treatment effects under ranibizumab.From December 2012 till June 2013 all patients receiving intravitreal injections of aflibercept after previous treatment with ranibizumab were collected in a database and retrospectively reviewed. Clinical data such as visual acuity or central subfield retinal thickness on optical coherence tomography (OCT) scans were analyzed for the time frame before, during, and shortly after the aflibercept injections. Of particular interest was the comparison of clinical features under ongoing ranibizumab treatment to the time during aflibercept treatment.Seventy-one eyes of 65 patients were included in the study. All eyes had previous ranibizumab injections in their medical history, the average number of which was nine (range 3-43). For the total group the mean visual acuity (VA) before the first ranibizumab injection was 0.54 logMAR, and after the last ranibizumab injection was 0.57 logMAR. Mean VA changed from 0.47 logMAR before the first aflibercept injection to 0.25 logMAR after the last aflibercept injection. Central subfield retinal thickness (CSRT) on OCT changed from a mean of 417.28 μm to 349.52 μm under ranibizumab treatment and from 338.76 μm to 272.00 μm under aflibercept treatment. Interestingly, 33 % of cases that did not show a functional improvement under ranibizumab therapy gained visual acuity after aflibercept treatment.Aflibercept appears to be an effective choice for patients with neovascular age-related macular degeneration who were resistant to previous therapy of ranibizumab. The longevity of this effect still remains questionable.

To characterize peripheral fundus autofluorescence (FAF) abnormalities in patients with age-related macular degeneration (AMD), correlate these with clinical findings, and identify risk factors associated with these FAF abnormalities.Clinic-based, cross-sectional study.A total of 119 consecutive patients: 100 patients with AMD (200 eyes) and 19 patients without AMD (38 eyes).In a prospective study performed at the Doheny Eye Institute, University of Southern California, widefield 200-degree FAF and color images were obtained by the Optos 200Tx Ultra-Widefield device (Optos, Dunfermline, Scotland) using a standardized imaging protocol. The FAF images were captured centered on the fovea, and additional images were captured after steering the field of view inferiorly and superiorly. All FAF and color images were graded independently by 2 masked ophthalmologists with respect to the presence, location, extent, and type of peripheral (defined as outside the central 30 degrees) FAF abnormality.Presence and type of peripheral FAF abnormalities.Peripheral FAF abnormalities were evident in 164 eyes (68.9%), with several distinct FAF patterns identified: granular (46.2%), mottled (34.0%), and nummular (18.1%). A 90% concordance of FAF patterns was observed between both eyes. Abnormal FAF occurred more frequently in neovascular compared with non-neovascular AMD or normal eyes (86% vs. 72.8% vs. 18.4%, respectively, P0.001). Significant risk factors for peripheral FAF abnormalities were AMD type (neovascular AMD odds ratio [OR], 12.7 and non-neovascular AMD OR, 6.2 compared with normal eyes, P0.001), older age (OR, 6.5; 95% confidence interval [CI], 2.4-17.8; P0.001 for the oldest quartile compared with the youngest), and female sex (OR, 4.1; 95% CI, 1.9-8.9; P0.001). Clinical features on color photography were detected in 174 eyes (73.1%): peripheral drusen (51.7%), retinal pigment epithelium (RPE) depigmentation (34.9%), RPE hyperpigmentation (branching reticular pigmentation) (22.7%), and atrophic patches (16.8%). There was a high correlation between specific FAF and clinical findings: granular FAF with peripheral drusen (P0.001) and mottled FAF with RPE depigmentation (P0.001).Several distinct patterns of peripheral FAF abnormalities were observed in 68.9% of patients, with AMD type, female sex, and age being independent risk factors. The peripheral FAF patterns correlate strongly with specific clinical features seen in eyes with AMD.Proprietary or commercial disclosure may be found after the references.

To present a selected case series of different phenotypes of the normal outer plexiform layer (OPL) visualized by optical coherence tomography (OCT).Five cases were selected to represent the spectrum of appearances of the OPL in this case series. Categorical descriptions of each manifestation were then developed. Additional SD-OCT scans were obtained from a normal volunteer to further support the hypothesis.The inner one-third of the OPL typically appears hyperreflective on OCT, while the outer two-thirds (Henle fiber layer) may have a more varied appearance. Six different phenotypes of Henle fiber layer reflectivity were noted in this series, and classified as: bright, columnar, dentate, delimited, indistinct, and dark. The brightness of the Henle fiber layer appears to depend on the geometric angle between the OCT light beam and the axonal fibers in this portion of the OPL. This angle appears to be a function of the natural orientation of the Henle fiber layer tissue (θN), the existence of subretinal pathology that alters the angle of the neurosensory retina (θ(P)), and the tilt angle of the tissue on the B-scan (θ(T)) due to decentered OCT acquisition.Since accurate interpretation of the OPL/ONL boundary is of vital importance to study the thickness of ONL, location of cystoid lesions, hyperreflective crescents over drusen, et al., our case series may aid better understanding of the OPL appearance in SD-OCT. In the absence of clear delineation, it may be most correct to refer to indistinct OPL and ONL together as the photoreceptor nuclear axonal complex (PNAC).

To assess the influence of varying B-scan frame-sampling densities on retinal thickness and volume measurements from spectral domain optical coherence tomography (OCT) in eyes with neovascular age-related macular degeneration (AMD). Volume OCT data (512 × 128 macular cube over 6 × 6 mm) were collected from 39 eyes with neovascular AMD. All 128 B-scans in each image set were manually segmented, allowing quantification of the neurosensory retina, subretinal fluid (SRF), subretinal hyperreflective material (SRHM), and pigment epithelium detachment (PED). Thickness maps were generated for less dense subsets of scans, ranging from every other (64 B-scans) to every 64th (2 B-scans). For each less dense subset, foveal central subfield thickness and total macular volume (TMV) were compared with values obtained using all 128 scans (considered the reference). For each parameter, the mean absolute difference compared with the reference increased with reducing B-scan density. However, these differences did not reach statistical significance until frame-sampling density was reduced to every eighth scan (ie, 16 B-scans spaced 375 μm apart) for neurosensory retina, and every fourth scan (ie, 32 B-scans spaced 188 μm apart) for SRF, SRHM, and PED. For neurosensory retina, the mean (% error) and maximum (% error) absolute differences in TMV were 0.02 mm3 (0.24%) and 0.06 mm3 (0.79%), respectively. Similarly, at a density of 32 B-scans, mean and maximum differences for SRF were 0.004 mm3 (3.47%) and 0.02 mm3 (22.22%), respectively. The mean differences for SRHM and PED were 0.01 mm3 (8.03%) and 0.01 mm3 (4.04%), respectively. A minimum of 16 equally spaced B-scans, covering a 6 × 6 mm area, appears necessary to generate retinal thickness measurements similar to those obtained using all 128 B-scans in eyes with choroidal neovascularization (CNV). When considering other CNV lesion features, a minimum of 16 B-scans for SRF and PED, and 32 B-scans for SRHM are required to generate volume maps similar to ground-truth values. These findings may have implications for the design of acquisition and grading protocols for clinical trials using OCT in neovascular AMD.

Age-related macular degeneration (AMD) is the leading cause of severe visual loss in people aged 50 years or older in the developed world. In recent years, major advances have been made in the treatment of AMD, with the introduction of anti-angiogenic agents, offering the first hope of significant visual recovery for patients with neovascular AMD. In line with these advances, a new imaging modality-optical coherence tomography (OCT)-has emerged as an essential adjunct for the diagnosis and monitoring of patients with AMD. The ability to accurately interpret OCT images is thus a prerequisite for both retina specialists and comprehensive ophthalmologists. Despite this, the relatively recent introduction of OCT and the absence of formal training, coupled with rapid evolution of the technology, may make such interpretation difficult. These problems are compounded by the phenotypically heterogeneous nature of AMD and its complex morphology as visualized using OCT. We address these issues by summarizing the current understanding of OCT image interpretation in patients with AMD and describe how OCT can best be applied in clinical practice.

Purpose The purpose of this study was to examine the functional and structural correlates of severe foveal dystopia in patients with epiretinal membranes. Methods For this retrospective study of 29 eyes with epiretinal membrane, we identified 7 eyes that had severe foveal dystopia (defined as fovea located >200 μm from its expected location) and followed the direction and rate of foveal movement pre- and postoperatively. Results Epiretinal membrane traction caused the fovea to move preoperatively at a rate of 275 μm/month from its anatomical location in 2 patients. The final preoperative foveal location was, on average, 1,217 ± 683 μm away from its expected location. Postoperatively, foveal movement toward its expected location was largest during the first month after surgery (mean = 547 ± 340 μm) and slowed down until the final follow-up position was achieved (mean = 301 ± 131 μm). Overall, the fovea moved a total of 848 ± 445 μm, allowing the fovea to correct only 32.8 ± 22.1% of the total displacement from its expected location. A univariate regression model confirmed a linear relationship between preoperative visual acuity and preoperative foveal distance from its expected anatomical location with an R2 of 0.759 (P = 0.0107). Conclusion The extent of tractional foveal dystopia correlates with decreased visual acuity. Although all patients experienced functional and anatomical improvements with surgery, long-standing or severe foveal dystopia may be associated with permanent structural changes that limit functional outcome. Cases with extreme degrees of foveal dystopia may benefit from early intervention to prevent irreversible structural and functional changes.

To compare the retinal morphological characteristics of eyes with choroidal neovascularisation (CNV) secondary to pathological myopia versus eyes with CNV secondary to age-related macular degeneration (AMD), using quantitative optical coherence tomography (OCT) subanalysis.Twenty-one eyes of 21 patients newly diagnosed as having CNV secondary to pathological myopia, and 43 consecutive cases of eyes with newly diagnosed subfoveal CNV secondary to AMD were retrospectively collected. In all patients, StratusOCT images and fluorescein angiograms (FA) were available for analysis. StratusOCT images were analysed using custom software (termed "OCTOR"), which allowed calculation of the thickness/volume of the neurosensory retina, subretinal fluid (SRF), subretinal tissue (SRT) and pigment epithelial detachments (PEDs). FA images were used to calculate CNV leakage area and CNV lesion size for each eye.The total volume of neurosensory retina in the pathological myopia group was significantly less than in the AMD group (7.10 (SD 0.50) mm3 vs 7.76 (0.93) mm3, p = 0.004). The total volume of SRF in the pathological myopia group was less than in the AMD group, but the difference was not statistically significant (0.33 (1.38) mm3 vs 0.55 (0.82) mm3, p = 0.434). The total volume of SRT in the pathological myopia group was less than in the AMD group, but the difference was not statistically significant (0.16 (0.15) mm3 vs 0.36 (0.60) mm3, p = 0.144). The total volume of PED in the pathological myopia group was markedly less than in the AMD group (0.01 (0.03) mm3 vs 1.09 (1.89) mm3, p0.001). On FA, the total leakage of CNV in the AMD group was significantly greater than in the pathological myopia group (4.17 (3.29) DAs vs 0.53 (0.58) DAs, p0.001).CNV lesions in pathological myopia were associated with considerably less retinal oedema, SRF and SRT compared with CNV associated with AMD. PEDs were almost negligible in myopic lesions compared with AMD. These findings are consistent with previous clinical and angiographic descriptions of myopic CNV as relatively small lesions with modest exudation.

To evaluate the long-term (1 year) functional and anatomical outcome of autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 30 patients with age-related macular degeneration (AMD).After the extraction of the neovascular complex, an autologous peripheral full-thickness graft of RPE and choroid was positioned under the macula. Functional tests included ETDRS vision, reading (Radner test), and microperimetry (scanning laser ophthalmoscope). Fluorescein, indocyanine green angiography, and autofluorescence were monitored.Preoperative visual acuity ranged from 20/40 to 20/800 (0.3-1.6 log MAR). Vision ranged from 20/25 to LP (0.1-2.1 log MAR) 1 year after surgery, with stabilization in six eyes, an increase in five eyes, and a decrease in 19 eyes. Deterioration mostly occurred within the first 3 months after surgery. In patients who demonstrated vascularization of the graft after 3 months, this persisted up to 12 months as did fixation when initially stable. Autofluorescence decreased significantly from 6 to 12 months postoperatively. Eleven cases showed a recurrence of choroidal neovascularization (CNV) within this period.Patch translocation results in a viable graft. There is no evidence of graft failure within a 1-year follow-up. Nevertheless, there is risk for late CNV formation originating from the edges of the excision side of the CNV and growing peripheral to the graft.

To determine the anatomical and functional outcome after injection of bevacizumab (Avastin, Genentech) in eyes with retinal angiomatous proliferation (RAP).Prospective interventional case series.Sixteen eyes of 16 consecutive patients with visual loss due to RAP underwent intravitreal injections of 1.25 mg (0.05 ml) bevacizumab. Best corrected visual acuity testing, fluorescein and ICG-angiography as well as OCT imaging were performed at baseline and at each follow-up visit within a 3-month period.Mean visual acuity pre-injection was 0.68 +/- 0.36 logMAR (n = 16), mean reading ability 0.58 +/- 0.26 logRAD (n = 11). Far vision increased significantly by a mean of 1.7 +/- 2 lines 4 weeks after the injection (p = 0.004), as did reading (0.6 +/- 2.3 lines, p0.05). Both remained stable up to 3 months. Central retinal thickness decreased from 367 +/- 112 microm (mean+/-SD) to 272 +/- 123 microm 3 months after injection (p = 0.006). Leakage decreased angiographically in 12 eyes (75%) and remained stable in four eyes (25%). Re-injection of bevacizumab within the 3-month follow-up period was performed once in eight eyes, and twice in one eye. No adverse events were observed.Intravitreal bevacizumab (Avastin) resulted in a reduction of leakage, intra- and subretinal fluid. An increase in visual acuity was seen already 4 weeks after first injection. However, a complete occlusion of feeder vessels could not be achieved within this 3-month period. Randomized clinical trials would be required to evaluate dose and frequency of injections and possible beneficial effects of combination therapies, as well as the long-term results.

Purpose To evaluate the functional and anatomical outcomes of autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in patients with geographic atrophy. Design Prospective nonrandomized study. Participants Twelve consecutive patients with geographic atrophy secondary to age-related macular degeneration presenting with recent loss of reading vision. Methods An autologous peripheral full-thickness graft of RPE, Bruch's membrane, and choroid was positioned under the macula in patients with geographic atrophy. Main Outcome Measures Functional tests included Early Treatment Diabetic Retinopathy Study distant vision, reading (Radner Test, measured as logarithm of the reading acuity determination [logRAD]), threshold static perimetry, and determination of the point of fixation. Fluorescein and indocyanine green angiography, autofluorescence, and optical coherence tomography served to evaluate the anatomical outcome in a 6-month follow-up (12 months in 7 patients). Results Preoperative visual acuity (VA) ranged from 20/800 to 20/40 (mean, 0.6±0.4 logarithm of the minimum angle of resolution), and reading vision from 1.1 to 0.5 logRAD (mean, 0.8±0.2). Three patients were unable to read. Six months after surgery, VA ranged from hand movements to 20/32, with an increase of ≥5 letters in 2 eyes. Two patients without reading ability preoperatively were able to read after surgery. Reading was possible in a total of 8 patients after 6 months (1.3–0.4 logRAD). In 7 patients who were observed for 1 year, VA remained stable (±1 line) in 5 eyes and decreased in 2 eyes between 6 months' and 1 year's follow-up. In all eyes but 2, revascularization was visible on indocyanine green angiography as early as 3 weeks after surgery. Autofluorescence of the RPE was independent of revascularization of the graft and persisted throughout follow-up. Four eyes had unstable fixation and/or extrafoveal fixation before surgery. Two of these eyes stabilized during follow-up. Areas overlying atrophic areas demonstrated low threshold sensitivities that persisted after translocation of a free graft with only limited recovery. Revisional surgery due to proliferative vitreoretinopathy was required in 5 eyes. Conclusions The translocation of a full-thickness graft usually results in a vascularized and functioning graft in patients with geographic atrophy, although is associated with a high risk of complications and visual loss. Longer follow-up is necessary to learn about the long-term survival and functionality of the graft.

Aim To identify the prevalence of self-reported non-ocular primary malignancies in patients at the time of diagnosis with uveal melanoma (UM) and to describe the cohort’s characteristics. Methods A data query for cases of UM seen at the Liverpool Ocular Oncology Centre between January 1993 and May 2014 was performed. Only patients who had UM with other non-ocular primary malignancies were included. Demographic and clinical data were analysed. Results A total of 5042 (2563 males, 50.8%) patients with UM were found in the database; of whom, 216 (4.3%) had at least one other primary non-ocular malignancy. Of these 216 patients, 119 were males (55.1%). Forty five males (37.8%) had been diagnosed with prostate cancer, 30 (25.2%) with unspecified skin cancers, 15 (12.6%) with colon and bowel carcinoma, eight (6.7%) with systemic lymphoma and the remaining patients with less common tumours. Of the 97 females, 45 (46.4%) had been diagnosed with breast carcinoma, 19 (19.6%) had unspecified skin cancers, seven (7.2%) renal cell carcinoma, six (6.2%) colon and bowel carcinoma, and the remaining patients had other less common tumour types. In this cohort, the frequency of the most common additional malignancy in male and female patients with UM was comparable with their prevalence in the general UK population. Conclusions Additional primary malignancies can occur in association with UM; therefore, medical history taking in patients with UM should always include this aspect. Apart from providing demographic and clinical data in such cases, future collaborative studies, which would include germline mutational testing, may reveal relevant common patterns.

Purpose To describe the clinical finding of subretinal fluid (SRF) in the posterior pole by spectral domain optical coherence tomography (SD-OCT) in eyes with active ocular toxoplasmosis (OT). Design Retrospective case series. Participants Thirty-eight eyes from 39 patients with active OT. Methods Eyes with active OT which underwent SD-OCT were reviewed. SRFs in the posterior pole were further analyzed. Main Outcome Measures Presence of SRF; its accompanying features, e.g. retinal necrosis, cystoid macular edema (CME), choroidal neovascularization (CNV); and longitudinal changes of SRF, including maximum height and total volume before and after treatment. Results SRF presented in 45.5% (or 15/33) of eyes with typical active OT and in 51.3% (or 20/39) of eyes with active OT. The mean maximum height and total volume of SRF were 161.0 (range: 23–478) µm and 0.47 (range: 0.005–4.12) mm3, respectively. For 12 eyes with SRF related to active retinal necrosis, SRF was observed with complete absorption after conventional anti-toxoplasmosis treatment. The mean duration for observation of SRF clearance was 33.8 (range: 7–84) days. The mean rate of SRF clearance was 0.0128 (range: 0.0002–0.0665) mm3/day. Conclusions SRF (i.e., serous retinal detachment) is a common feature in patients with active OT when SD-OCT is performed. The majority of SRF was associated with retinal necrosis and reacted well to conventional therapy, regardless of total fluid volume. However, SRF accompanying with CME or CNV responded less favorably or remained refractory to conventional or combined intravitreal treatment, even when the SRF was small in size.

Background Recently it was suggested that high myopia macular holes (HMMH) and macular holes accompanied by retinal detachment occur in the advanced stages of myopia traction maculopathy (MTM), while macular retinoschisis, shallow retinal detachment without holes, and lamellar macular holes occur in the early stages of MTM. Complete vitreous cortex removal associated with internal limiting membrane peeling is now widely used to treat HMMH. However, it remains uncertain at what HMMH stage patients would benefit most from surgical intervention. Our study was aimed to evaluate the postoperative anatomical changes and functional outcomes of high myopia macular holes (HMMH). Methods Patients were retrospectively collected between March 2009 and August 2011. Before and 1st, 3rd, and 9th month after 23G pars plana vitrectomy, all patients underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT) and MP-1. At each follow-up, best- corrected visual acuity (BCVA), photoreceptor inner and outer segments (IS/OS) defects, and retinal sensitivity (RS) were investigated. According to different preoperative macular hole morphologies, patients were divided into three groups: Group 1, macular hole with epiretinal membrane (ERM) traction and macular retinoschisis; Group 2, full-thickness macular hole (FTMH); Group 3, FTMH with subretinal fluid. Results 43 eyes from 43 patients met the inclusion criteria. The mean age was 60 years. BCVA and RS were significantly improved after vitrectomy; the mean IS/OS defect was significantly reduced. At 9 postoperative months, 11 of 43 (25.6 %) eyes achieved IS/OS junction integrity; 9 of these 11 (81.8 %) eyes belonged to Group 1, 2 (18.2 %) belonged to Group 2. Conclusions Pars plana vitrectomy combined with ILM peeling and gas tamponade results in limited functional outcomes in patients with HMMH. The appearance of subretinal fluid indicates a worse prognosis for surgical intervention.

Background Recently it was shown that retinal vessel diameters could be measured using spectral domain optical coherence tomography (OCT). It has also been suggested that retinal vessels manifest different features on spectral domain OCT (SD-OCT) depending on whether they are arteries or veins. Our study was aimed to present a reliable SD-OCT assisted method of differentiating retinal arteries from veins. Methods Patients who underwent circular OCT scans centred at the optic disc using a Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were retrospectively reviewed. Individual retinal vessels were identified on infrared reflectance (IR) images and given unique labels for subsequent grading. Vessel types (artery, vein or uncertain) assessed by IR and/or fluorescein angiography (FA) were referenced as ground truth. From OCT, presence/absence of the hyperreflective lower border reflectivity feature was assessed. Presence of this feature was considered indicative for retinal arteries and compared with the ground truth. Results A total of 452 vessels from 26 eyes of 18 patients were labelled and 398 with documented vessel type (302 by IR and 96 by FA only) were included in the study. Using SD-OCT, 338 vessels were assigned a final grade, of which, 86.4% (292 vessels) were classified correctly. Forty three vessels (15 arteries and 28 veins) that IR failed to differentiate were correctly classified by SD-OCT. When using only IR based ground truth for vessel type the SD-OCT based classification approach reached a sensitivity of 0.8758/0.9297, and a specificity of 0.9297/0.8758 for arteries/veins, respectively. Conclusion Our method was able to classify retinal arteries and veins with a commercially available SD-OCT alone, and achieved high classification performance. Paired with OCT based vessel measurements, our study has expanded the potential clinical implication of SD-OCT in evaluation of a variety of retinal and systemic vascular diseases.

Purpose: To compare drusen measurements obtained from color fundus and infrared retromode photographs with those derived from spectral-domain optical coherence tomography. Methods: Drusen lesions identified on the planar (color and infrared) imaging modalities were manually segmented by two independent graders using previously described reading center software to produce quantitative measurements of drusen area and number. The corresponding volume Cirrus OCT datasets were analyzed using commercial retinal pigment epithelium analysis algorithms to segment the retinal pigment epithelium band and estimated the drusen area. Drusen numbers were extracted from retinal pigment epithelium elevation maps. Intraclass correlation coefficients assessed agreement between graders; graders' average measurements were compared with optical coherence tomography (OCT) using paired T-tests. Results: Excellent agreement between graders was observed (r = 0.951–0.974). No statistical difference was found in the area values obtained by color (0.85 ± 0.26 mm2, P = 0.43) or retromode (1.15 ± 0.32 mm2, P = 0.35) compared with those obtained by OCT (0.98 ± 0.28 mm2). The number of drusen identified by OCT (13.15 ± 3.19) was significantly lower than that determined by manual segmentation of color (53.7 ± 13.18) and retromode (100.13 ± 16.18) images. Conclusion: Although the number of drusen individualized by commercial OCT algorithms is significantly lower than by planar fundus imaging modalities, the OCT-measured drusen area is not affected, suggesting that the algorithm counts confluent drusen as a single drusen.

PURPOSE: To determine the sensitivity of three-dimensional optical coherence tomography (3D-OCT) versus single field nonmydriatic fundus photography (FP) for detection of a variety of retinal abnormalities. METHODS: Images from consecutive patients in a retina clinic undergoing simultaneous 3D-OCT (512 × 128) and single, foveal nonmydriatic 45° color fundus imaging with 3D-OCT-1000 in a 4 month-period were retrospectively collected. Findings from each modality were graded independently by two graders as present, questionable, or absent. Irregularities were separated into three categories for intermodality comparisons: epiretinal, retinal/subretinal, and RPE/choroidal irregularities. The approximate location of findings in relation to the 3D-OCT field was noted as in field and out of field. Findings from both modalities were combined to form the gold standard for comparison for each modality. RESULTS: Five hundred and one sets of 3D-OCT scans and fundus images of 395 eyes of 223 patients were found in the study period, of which, 474 unique visits were included. Ninety-six percent of the scans had abnormal findings. Twenty-six fundus images (5.5%) were ungradable. 3D-OCT identified some abnormality in 25/26 (96.2%) of the ungradable fundus images. For overall detection of a variety of retinal irregularities or irregularity of each category (epiretinal, intraretinal, or RPE/choroidal irregularity), 3D-OCT was found to be more sensitive than that of nonmydriatic color fundus images. When single specific feature was speculated, 3D-OCT demonstrated various detection abilities: higher than FP for abnormal retinal thickness (or intraretinal hyporeflective features); similar as FP for RPE atrophy; however, lower for pigment migration (or intraretinal hemorrhage). CONCLUSIONS: In this study, sensitivities of 3D-OCT were higher than nonmydriatic fundus images for overall detection of retinal abnormalities or irregularities in each category. 3D-OCT demonstrated good ability to detect most features; however, with limitation to intraretinal hemorrhage and pigment migration. It is likely that OCT will be added to photography screening for chorioretinal diseases in the near future.

Purpose To use spectral domain optical coherence tomography (SD-OCT) to investigate risk factors predictive for the development of atrophy of drusenoid lesions (DLs) (drusen and drusenoid pigment epithelium detachment) in eyes with non-neovascular age-related macular degeneration (NNVAMD). Design Cohort study. Participants Forty-one eyes from 29 patients with NNVAMD. Methods Patients with NNVAMD who underwent registered SD-OCT imaging over a minimum period of 6 months were reviewed. Drusenoid lesions that were accompanied by new atrophy onset at 6 months or last follow-up (FUL) were further analyzed. Detailed lesion change was described throughout the study period. Odds ratios (ORs) and risk for new local atrophy onset were calculated. Main Outcome Measures Drusenoid lesion features and longitudinal changes in features, including maximum lesion height, lesion diameter, lesion internal reflectivity, and presence and extent of overlying intraretinal hyperreflective foci (HRF). Subfoveal choroidal thickness (SFCT) and choroidal thickness (CT) were measured below each lesion. Results A total of 543 individual DLs were identified at baseline, and 28 lesions developed during follow-up. The mean follow-up time was 21.3±8.6 months (range, 6–44 months). Some 3.2% of DLs (18/571) progressed to atrophy within 18.3±9.5 months (range, 5–28 months) of the initial visit. Drusenoid lesions with heterogeneous internal reflectivity were significantly associated with new atrophy onset at 6 months (OR, 5.614; 95% confidence interval [CI], 1.277–24.673) and new atrophy onset at FUL (OR, 7.005; 95% CI, 2.300–21.337). Lesions with the presence of HRF were significant predictors of new atrophy onset at 6 months (OR, 30.161; 95% CI, 4.766–190.860) and FUL (OR, 11.211; 95% CI, 2.513–50.019). Lesions with a baseline maximum height >80 μm or CT ≤135 μm showed a positive association with the new atrophy onset at FUL (OR, 7.886; 95% CI, 2.105–29.538 and OR, 3.796; 95% CI, 1.154–12.481, respectively). Conclusions The presence of HRF overlying DLs, a heterogeneous internal reflectivity of these lesions, was found consistently to be predictive of local atrophy onset in the ensuing months. These findings provide further insight into the natural history of anatomic change occurring in patients with NNVAMD. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

PURPOSE To compare the sensitivity of volume scanning with optical coherence tomography (OCT) to nonmydriatic color fundus photography (FP) for the detection of retinal irregularities in asymptomatic populations. METHODS Asymptomatic subjects without known ocular disease were recruited over a 6-month period. For each eye, two undilated 45° fundus images and four undilated volume OCT image sets covering the macula and optic nerve were obtained. Color images were evaluated for irregularities both inside and outside the area covered by OCT. OCT image sets were evaluated for internal limiting membrane irregularities, abnormal retinal thickness, hyper/hyporeflective features, and photoreceptor/retinal pigment epithelium (RPE) irregularities. Detection sensitivities were compared and false-negative cases were analyzed. RESULTS A total of 284 eyes (144 subjects) were included, with a mean age of 38.1 years (range 18-77). Among 253 eyes (135 subjects) with gradable images from both FP and OCTs, the detection sensitivities for OCT were higher (96.2% infield and 85.7% in full field) than for FP (19.9% infield and 43.8% in full field) for all irregularities evaluated in the study (including epiretinal irregularities, abnormal retinal thickness, intraretinal hyperreflective/hyporeflective features, and photoreceptor/RPE irregularities). Overall, the presence of definite irregularities on either fundus imaging or OCT by eye in this asymptomatic population was 42.6% (121/284), with 39.4% (112/284) of eyes having RPE irregularities such as drusen. CONCLUSIONS For detection of a variety of retinal irregularities evaluated in the current study, volume OCT scanning was more sensitive than nonmydriatic retinal photography in our asymptomatic individuals. OCT detected clinically relevant disease features, such as subretinal fluid, that were missed by FP, and had a lower ungradable image rate. It is likely that OCT will be added to photography screening in the near future for chorioretinal disease.

PURPOSE: To assess the accuracy of automated classification of pigment epithelial detachments (PED) by using a software algorithm applied to spectral-domain optical coherence tomography (SD-OCT) scans. METHODS: HD-OCT (Cirrus; Carl Zeiss Meditec, Dublin, CA) volume scans (512 × 128) were retrospectively collected from 46 eyes of 33 patients with evidence of PED in the setting of age-related macular degeneration (AMD, n = 28) or central serous chorioretinopathy (CSCR, n = 5). In these eyes, 168 PEDs were automatically detected with a system-associated tool (Cirrus HD-OCT RPE Elevation Analysis; Carl Zeiss Meditec). Two independent, certified Doheny Image Reading Center (DIRC) OCT graders classified these PEDs into three categories--serous, drusenoid, or fibrovascular--via inspection of the B-scans. Manual classification results served as the gold standard for comparisons with automated classification. For automated classification, interindividual variation in intensities was normalized in all images. Individual A-scans within the detected PEDs were then automatically classified into one of three categories based on the mean internal intensity and the standard deviation of the internal intensity: mean intensity

Recurrence of herpetic keratitis and immune reactions is the major cause of graft failures after penetrating keratoplasty as a consequence of herpes simplex keratitis. No treatment regimen is yet considered a standard of care. This retrospective study analyzes the effectiveness of combined systemic acyclovir and immunosuppressive therapy with cyclosporine A (CSA) or mycophenolate mofetil (MMF) after high-risk keratoplasty in herpetic keratitis.A total of 87 high-risk keratoplasties treated with postoperative combined systemic acyclovir and immunosuppressive therapy with CSA or MMF were analyzed retrospectively according to the therapeutic regimen, the degree of preoperative corneal vascularization, and tissue matching of the graft. Endpoints included immunological graft rejection, recurrence of the herpetic keratitis, graft failure, and visual acuity.There was an overall trend toward an improvement of visual acuity. Graft failure occurred in 13.1%, in all cases after termination of immunosuppression with MMF or CSA. In 4 of 11 cases, immune reactions caused graft failure. Patients with 3 to 4 quadrants of corneal vascularization showed significantly higher rates of graft rejection than patients with 1 to 2 quadrants vascularized or avascular corneas. Herpetic recurrence occurred in 31.8% and caused 18.2% of graft failure. In 7 of 23 cases, graft rejection was induced by herpetic recurrence.Graft survival rate and functional outcome after postoperative antiviral and immunosuppressive treatment in cases of penetrating keratoplasties after herpetic keratitis are comparable with results of normal-risk keratoplasties, despite existing high risks for immune rejections or herpetic recurrences.

Background/aims To compare retinal thickness measurements from three different spectral domain optical coherence instruments when manual segmentation is employed to standardise retinal boundary locations. Methods 40 eyes of 21 healthy subjects were scanned on the Cirrus HD-OCT, Topcon 3D-OCT-2000 and Heidelberg Spectralis-OCT. Raw data were imported into custom grading software (3D-OCTOR). Manual segmentation was performed on every data set, and retinal thickness values in the foveal central subfield were computed. Results 37 eyes of 20 subjects were gradable on every machine. The average retinal thicknesses for these eyes were 236.7 μm (SD 20.1), 235.7 μm (SD 20.4) and 236.5 μm (SD 18.0) for the Cirrus, 3D-OCT-2000 and Spectralis, respectively. Comparing manual retinal thickness measurements between any two machines, the maximum difference was 18.2 μm. The mean absolute differences per eye between two machines were: 4.9 μm for Cirrus versus 3D-OCT-2000, 3.7 μm for Cirrus versus Spectralis and 4.4 μm for 3D-OCT-2000 versus Spectralis. Conclusions When a uniform position is used to locate the outer retinal boundary, the retinal thickness measurements derived from three different spectral domain optical coherence instruments devices are virtually identical. Manual correction may allow OCT-derived thickness measurements to be compared between devices in clinical trials and clinical research.

BACKGROUND AND OBJECTIVE: To assess the prevalence of peripheral fundus autofluorescence (FAF) abnormalities in chronic Vogt-Koyanagi-Harada disease (VKH). PATIENTS AND METHODS: A retrospective review of cases at the Doheny Eye Institute between December 2009 and April 2010. Patients with chronic VKH who had ultra-wide–field FAF and pseudo-color imaging performed were included. All images were reviewed independently by two reading center certified retina specialists. RESULTS: Twenty eyes of 10 patients were included in this analysis. Fourteen eyes of 7 patients (70%) showed peripheral changes on FAF images outside the posterior pole. Three different patterns were observed: multifocal hypofluorescent spots (n = 11 eyes), hyperfluorescent spots (n = 8 eyes), and a unique lattice-like pattern in both eyes of one patient. There were noticeable disparities between FAF and color images. CONCLUSION: Peripheral FAF abnormalities are frequent in chronic VKH and are readily revealed by wide-field FAF imaging and manifesting with distinct patterns. Further investigation in prospective studies is warranted.

Aims: To determine the characteristics of “non-responders” to intravitreal bevacizumab treatment in choroidal neovascularisation (CNV). Methods: Forty-three patients with visual loss due to neovascular age-related macular disease (ARMD) (44 eyes) underwent intravitreal injections of 1.25 mg (0.05 ml) bevacizumab and were followed up every 4 weeks for 2, 3 or 6 months. Re-injection was performed when persistent leakage of the CNV was determined by fluorescein angiography and retinal oedema was assessed by optical coherence tomography (OCT). Non-responders were defined as those patients having reduced or stable visual acuity at the last follow-up. Results: 45% of the patients were non-responders. In this group the initial CNV size was significantly larger than in the responders. Initial reading ability was significantly lower in non-responders, but the initial foveal oedema was similar in both groups. Gains in mean visual acuity and reading ability were independent of lesion type. The proportion of non-responders to responders in the different lesion type groups was equally distributed. Only patients with the classic type of CNV seemed to respond better. Conclusions: In this study initial reasons for non-responders to intravitreal bevacizumab treatment in CNV are given. The efficiency of bevacizumab depends on initial lesion size and initial reading ability, but is independent of the amount of intraretinal and subretinal fluid. There was no general ineffectiveness of bevacizumab with any particular lesion type.

To analyse structural changes after autologous translocation of choroid and retinal pigment epithelium (RPE) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT).We performed a prospective nonrandomised study in 29 consecutive patients, who underwent submacular surgery with translocation of an autologous full-thickness graft of RPE, Bruch's membrane, and choroid. All patients had recent loss of reading vision due to AMD. OCT was performed before surgery and at 3- and 6- month follow-up to analyse the morphological appearance of the graft and the overlying retina.Maximum retinal thickness decreased from mean 408 microm (standard deviation (SD) 127 microm) preoperative to mean 373 microm (SD 104 microm) at 6-month follow-up (P=0.094). In 11 cases (40%), a nearly physiological shape of the retina was seen at this time point. A macular hole persisted in two eyes after silicone oil removal. In most eyes, the highly reflective band of the graft presumably corresponding to RPE was continuous with the surrounding RPE band in all six OCT scans. Eyes with flat appearance of the graft at 6-month follow-up (300 microm) showed a significantly better functional outcome than eyes with more prominent grafts. Interestingly, most patients did not complain about metamorphopsia, even though the graft was prominent or wrinkled in some cases.OCT is a useful tool in monitoring intra- and subretinal changes after subretinal surgery with graft translocation. We demonstrated that graft translocation may lead to a normalisation of retinal thickness and stabilisation of visual acuity.

Purpose To compare the optical coherence tomographic (OCT) correlates of two previously described angiographic subtypes of occult choroidal neovascularization (CNV). Methods We retrospectively analyzed 17 consecutive patients with previously untreated occult CNV who underwent both fluorescein angiography (FA) and volume spectral domain (SD)-OCT imaging on the same visit. Planimetric grading was performed on the FA images by certified reading center graders to precisely outline the boundaries of the fibrovascular pigment epithelial detachment (FVPED) and/or late leakage of undetermined source (LLUS) components of occult CNV for each case. In the SD-OCT images, the outer retinal pigment epithelial (RPE) and inner choroidal boundaries were manually segmented on all B-scans to generate a PED thickness map. Fluorescein angiography images were manually registered with the OCT fundus image, and the PED thickness was correlated with the angiographic lesion component present at each corresponding point in the fundus. Results Point-to-point correlations revealed that PED thickness was significantly different in areas of FVPED versus areas of LLUS. Whereas the mean PED thickness in areas of FVPED was 196.1 ± 120.36 μm, it was only 38.42 ± 8.14 μm in areas of LLUS (P = 0.003). Normalized internal reflectivity in areas of FVPED was lower than in areas of LLUS (0.12 ± 0.11 vs. 0.24 ± 0.07; P = 0.03). The integrity or continuity of the overlying RPE band on OCT, however, did not appear to differ between areas of LLUS and FVPED (P = 0.33). Conclusions Although LLUS and FVPED appear to be distinct angiographic subtypes of CNV, the major difference between the two is the height of the RPE elevation and the internal reflectivity, with areas of LLUS representing much shallower RPE elevations with brighter mean internal reflectivity.

To use three-dimensional optical coherence tomography (3D-OCT) to assess the prevalence of juxtapapillary retinal pigment epithelial detachments (jPED) in an asymptomatic population.Asymptomatic participants (i.e., family members of patients) were prospectively recruited over a 6-month period. Each subject completed a questionnaire prior to the acquisition of two undilated 45° fundus images and two undilated raster 3D-OCT scans (512 × 128) covering the macula and optic nerve from each eye using 3D-OCT-1000. Fundus images were graded for the presence of peripapillary atrophy (PPA), peripapillary pigment (PPP), drusen in the macula, and drusen elsewhere, whereas 3D-OCT scans were assessed for the presence of jPED, drusen in the macula, and drusen elsewhere.In all, 276 eyes from 138 participants were evaluated. Mean participant age was 37.6 years (range: 18-74 years; SD: 15.5 years). In all, 87 jPEDs were detected in 26.1% (36/138) of asymptomatic participants (25 bilateral and 11 unilateral) or 17.0% (47/276) of asymptomatic eyes (23 in the right eye and 24 in the left). The maximum height of jPED was 198.3 ± 53.8 (range: 101.8-376.0) μm. The minimum distance of jPED to the border of optic nerve head (OPN) was 2.6 ± 11.1 (range: 0-61.9) μm. The occurrence of jPEDs or drusen elsewhere by subjects increased statistically with increasing age (P0.001, respectively).In this study, definite jPEDs were observed by OCT in asymptomatic participants, which were not seen with fundus photography. jPEDs were seen more commonly with increasing age, although it is not known whether these lesions represent deposition of drusen-like material or aborted choroidal neovascularization adjacent to the natural break in Bruch's membrane at the optic disc.

Purpose Evaluation of the effect of angle of incidence on macular thickness and volume measurements obtained by spectral-domain optical coherence tomography (OCT). Methods A total of 30 eyes from 15 healthy young subjects underwent macular cube volume scans (512 × 128 protocol) following dilation using the Cirrus spectral domain OCT. For each eye, scans were obtained by positioning the scanning beam in the center of the dilated pupil, as well as in four eccentric positions (approximately 3 mm from the center), superior, inferior, nasal, and temporal to the pupillary center, to create oblique angles of incidence between the light beam and retina. In all cases, the region scanned by the volume cube was centered on the fovea. Macular thickness and volume measurements were computed for volume scan acquisitions, and differences in values between eccentric scans and the central scan were analyzed. Results Retinal thickness and volume values were observed to increase significantly in all subfields for all eccentrically-obtained scans compared to scans obtained through the center of the pupil. The mean increase in thickness for the various scan positions and subfields ranged from 3.76 to 11.38. Scans that were displaced temporally consistently showed the greatest increase in thickness and volume, whereas nasally positioned scans showed the least increase. The increase in retinal thickness for all subfields correlated significantly with angle of inclination or tilting of the retina. Conclusions Macular thickness and volume measurement results may be affected significantly by positioning of the scanning beam in the pupil and resultant angle of incidence on the retina. These findings suggest that care should be taken to position the scanning beam consistently in the center of the pupil to achieve reliable measurements.

Purpose To identify visually significant spectral-domain optical coherence tomography (SD-OCT) features of epiretinal membranes (ERM) in patients with uveitis. Design Retrospective cohort and cross-sectional study. Methods Eighty consecutive eyes with uveitis and SD-OCT–documented ERM were included. Clinical data were collected at the time of diagnosis of ERM and at the final visit. SD-OCT images at the last visit were evaluated to identify fovea and ERM configuration and structural changes. Changes of 10% and 20% in central subfield thickness between initial and last SD-OCT were calculated and correlated with visual acuity (VA). An ERM thickness map was created using validated SD-OCT grading software. Results VA improved significantly in eyes with more than 12 months of follow-up ( P = .03). Although inflammation activity and medical treatment methods were no different in eyes with more or less than 12 months of follow-up, 16 eyes in the subset with longer follow-up underwent cataract extraction and intraocular lens implantation. Kaplan-Meier analysis demonstrated few vision losses during the follow-up period. Change in central subfield thickness did not correlate with VA. Foveal center involvement ( P P = .003), and foveal inner segment and outer segment junction disruption ( P = .006) were associated independently with lower VA. ERM was thinner in eyes with 20/40 or better VA (4.6 ± 0.6 μm) compared with eyes with VA of less than 20/200 ( P = .02). Longer duration of ERM was associated with thicker ERM ( P Conclusions In most eyes with uveitis and ERM, VA remains stable if ocular inflammation and comorbidities are addressed appropriately.

Bevacizumab (Avastin, Genentech, South San Francisco, CA), an antiangiogenic agent licensed for the management of colorectal carcinoma, has been widely adopted for the treatment of neovascular age-related macular degeneration (AMD).1,2 Recently, the results of the Avastin (Bevacizumab) in Choroidal Neovascularization (ABC) Trial provided the first level I evidence (i.e., evidence from a well-designed, randomized, controlled clinical trial) for the safety and efficacy of this approach.3 In the ABC trial, bevacizumab was administered as an intravitreous injection once every 6 weeks, after an initial loading phase of three intravitreous injections, further treatment was determined in large part by the assessment of disease activity using optical coherence tomography (OCT). As in the ABC study, many clinical trials have adopted OCT-derived retreatment criteria, both for neovascular AMD and for other disorders.4–6 In addition, the application of OCT to clinical research has elucidated many hitherto unrecognized disease characteristics and clarified many aspects of disease pathophysiology.7 The advent of OCT has also allowed objective, quantitative assessment of morphologic parameters,8,9 with OCT-derived measurements of retinal thickness commonly used for both clinical and research purposes.10,11 As our knowledge of OCT image analysis has grown, however, it has become increasingly clear that even accurate measurements of retinal thickness may fail to predict visual outcomes.12,13 Thus, much of the focus of recent clinical imaging research has been on the identification of novel OCT-derived anatomic biomarkers.14–17 For clinical trials, the discovery of novel OCT biomarkers may provide valuable information regarding therapeutic mechanisms of action, pharmacodynamics, and pharmacokinetics.18,19 If such biomarkers are shown to predict clinical benefit, they could also serve as surrogate endpoints in these trials, potentially leading to increased accuracy, reduced costs, and shortened duration. Similarly, in clinical practice, such parameters could extend the application of OCT imaging beyond simple diagnosis and toward prognosis.7 With the increased utilization of combination treatment strategies20 and the likely future development of additional pathway-based therapies,21 such pharmacodynamic and prognostic information may soon be crucial for the clinician in choosing the appropriate type and level of care. In the ABC trial, bevacizumab was compared to the standard therapy available at the trial's initiation: pegaptanib (Macugen; OSI Pharmaceuticals, New York, NY) or verteporfin photodynamic therapy (PDT; Novartis, Basel, Switzerland).3,22 Although treatment of patients in these standard therapy groups was not determined by OCT-derived criteria, OCT examinations were nonetheless performed. Thus, the ABC trial offers a unique opportunity to investigate novel OCT biomarkers, with an emphasis on differential pharmacodynamic effects, in a phase III/IV randomized clinical trial.

Imaging data have been an integral part of both ophthalmic clinical practice and clinical trials for decades. Despite the enthusiastic adoption of optical coherence tomography (OCT) into clinical practices over the last decade, the use of OCT in clinical trials has generally lagged behind its clinical use. For example, time domain OCT took years to become commonplace in neovascular age-related macular degeneration (NVAMD) clinical trials, in part because of inconsistencies in measurements due to software segmentation and registration irregularities in this disease.1–3 In the recent era of spectral domain OCT (SD-OCT), large data sets, a multitude of device manufacturers, and segmentation errors may again have hampered rapid integration of SD-OCT data into multicenter studies. Given the widespread adoption of SD-OCT into practices, continued failure to use this same technology in clinical trials maintains a disconnect between trials and practice that may interfere with the evidence-based management and therapy that often constitute the goal of these trials. Instead, it seems that a desirable goal for clinical trials should be to use and study techniques that can be readily adapted to clinical practice to guide patient management based on the conclusions from those trials. One OCT-based measure that has been used in both clinical trials and clinical practices is the automated report produced by each commercial OCT instrument.4–7 Despite the differences in measurements made by different machines, these data, such as macular volume and Early Treatment Diabetic Retinopathy Study grid retinal thickness measurements, have been useful in clinical trials because they provide a simple, objective, numerical distillation of the imaging data contained in the SD-OCT data set. However, these measurements are still prone to segmentation errors and fail to extract much of the rich data concerning specific lesions that are contained in OCT images.8–10 One common tool that is used in clinical trials but not in clinical practice is a reading center assessment. These evaluations extract data, such as the presence of cystoid macular edema (CME), subretinal fluid (SRF), or pigment epithelial detachments (PEDs), that may be overlooked by automated measurements. Based on the expertise of human graders, reading center assessments can detect and sometimes correct segmentation errors. However, the standardized training, protocols, and time involved in these assessments make them impractical for most clinicians. The goal of this study was to investigate simplified, quantitative methodologies that approach the accuracy of a detailed, time-consuming reading center assessment but can be completed in a short enough time to make it practical for most clinicians.

The choroid, a vascular meshwork between the retina and sclera, plays a major role in providing oxygen and nutrition to the outer layers of the retina.1 In recent years, increased awareness of its role in ocular development and its known association with many diseases of the posterior pole have stimulated a renewed focus on understanding choroidal anatomy and physiology.2 A number of methods, including histology3 and ultrasonography,4 have previously been used to quantify choroidal thickness (CT); however, the overall precision of these approaches is still lacking. Fortunately, the recent introduction of spectral domain optical coherence tomography (SD-OCT) and the description of “enhanced depth imaging” scanning protocols have afforded a new opportunity to improve the accuracy of quantitative choroidal assessment. As a result, changes in CT have now been studied using different OCT technologies over a wide range of ocular pathologies (e.g., glaucoma,5 inherited retinal diseases,6 high myopia,7 central serous chorioretinopathy,8 polypoidal choroidal vasculopathy,9 neovascular age-related macular degeneration [AMD],9 and Vogt Koyanagi Harada disease10). Although the use of OCT has provided many new insights into choroidal morphology, to date there exists a notable disparity between the CT measurements obtained in different studies. For example, several studies on the cross-sectional variation of CT measurements in “normal” subjects have shown CT to be greatest at the fovea, with decreasing thickness more nasally than temporally.9,11,12 Other results suggest that the foveal CT is thinner than the choroid superior to the fovea.13 These discrepancies may arise due to the use of different image acquisition methodologies, a generally limited field of view for scanning, and inconsistencies in choosing the exact locations for repeated CT measurement. Regardless, the exact spatial distribution of CT changes in the macular region of human eyes remains unclear. In addition, most OCT-derived studies have focused on assessment of CT in the macular region alone, examining the correlation between macular CT changes and disease expression. However, unlike the neurosensory retina, a complex and highly organized neural structure with the fovea as its unmistaken center, the choroid is a vascular layer with a potentially very different topography. Determination of choroidal spatial distribution may thus be difficult, and potentially inaccurate, in the context of macular scanning alone. In this report, we aim to address these issues by obtaining larger, two-dimensional (2D) maps of the spatial distribution of the choroid in the posterior pole and identifying its specific patterns in healthy volunteers using SD-OCT.

PURPOSE. To investigate the effects of ranibizumab on retinal morphology in patients with neovascular age-related macular degeneration (AMD) using optical coherence tomography (OCT) quantitative subanalysis. METHODS. Data from 95 patients receiving intravitreal ranibizumab for neovascular AMD were collected. StratusOCT images were analyzed using custom software that allows precise positioning of prespecified boundaries on every B-scan. Changes in thickness/volume of the retina, subretinal fluid (SRF), subretinal tissue (SRT), and pigment epithelial detachments (PEDs) at week 1 and at months 1, 3, 6, and 9 after treatment were calculated. RESULTS. Total retinal volume reached its nadir at month 1, with an average reduction of 0.43 mm 3 (P 0.001). By month 9, this initial change had been reduced to a mean reduction of 0.32 mm 3 (P 0.0011). Total SRF volume reached its lowest level by month 1, with an average reduction of 0.24 mm 3 (P 0.001). This reduction lessened subsequently, to 0.18 mm 3 ,b y month 9. There was an average 0.3-mm 3 decrease in total PED volume by month 1 (P 0.001), and this later declined further, to 0.45 mm 3 , by month 9 (P 0.0014). Total SRT volume was reduced by an average of 0.07 mm 3 at month 1 (P 0.0159) and subsequently remained constant. CONCLUSIONS. Although neurosensory retinal edema and SRF showed an early reduction to nadir after the initiation of ranibizumab therapy, the effect on the retina was attenuated over time, suggesting possible tachyphylaxis. PED volume showed a slower but progressive reduction. Manual quantitative OCT subanalysis may allow a more precise understanding of anatomic outcomes and their correlation with visual acuity. (Invest Ophthalmol Vis Sci. 2008;49:3115‐3120) DOI:10.1167/ iovs.08-1689

Purpose To evaluate the autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related macular degeneration (AMD). Design Prospective nonrandomized study. Methods All patients had visual loss due to AMD (n = 5 classic membranes, n=14 occult, n=2 mixed, n=16 pigment epithelial detachment (PED), n=5 subretinal hemorrhage, n=3 geographic atrophy). After extraction of the neovascular complex, an autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid was translocated from the midperiphery to the macula. Results Preoperative distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4 logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32 Snellen equivalent). Revision surgery was required in 22 eyes as a result of proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or vitreous hemorrhage. In eight patients, the patch was renewed. At six months, distant visual acuity ranged from light perception to 20/50 (increase of 15 letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual outcome was unrelated to the type of AMD. Vascularization of the transplant was visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most patients, autofluorescence of the pigment epithelium was coincident with revascularization of the graft. Fixation on the patch was positively related to visual acuity. Conclusions Autologous translocation of a full-thickness transplant of choroid and RPE usually results in a vascularized and functioning graft. Vascularization was even achieved in patients with geographic atrophy. Fixation stability and microperimetry before the patch translocation may be helpful in selecting patients who will profit from surgery.