Pearse A. Keane

Spatial distribution of posterior pole choroidal thickness by spectral domain optical coherence tomography.

PURPOSEnTo study the spatial distribution of posterior pole choroidal thickness (CT) in healthy eyes using spectral domain optical coherence tomography (SD-OCT).nnnMETHODSnFifty-nine eyes from 30 subjects with no retinal or choroidal disease were examined with high-definition (HD) OCT using macular volume cube scanning protocols. A randomly chosen subset also had multifield analysis performed (volume scans centered on and surrounding the optic nerve head [ONH]). CT was manually quantified using a validated reading center tool. For macular scans, mean CT was calculated for each Early Treatment Diabetic Retinopathy Study subfield. Compound posterior pole CT maps were also created through the alignment of OCT projection images. Regression analyses were used to evaluate the correlation between CT and axial length (AL), refractive error, age, sex, and ethnicity.nnnRESULTSnSubfoveal CT was 297.8 ± 82.2 μm, which did not differ significantly from that of the inner macular subfields. CT was greatest in the superior outer subfield and thinnest in the nasal outer subfield. The most predictive models for macular CT included AL and/or age. Outside the macula, CT was thinnest inferonasal to the ONH.nnnCONCLUSIONSnCT demonstrates large variations between individuals, but also at different locations within the posterior pole; substantial choroidal thinning inferonasal to the ONH was demonstrated. CT appears to correlate more with distance from the optic nerve than from the fovea and, thus, in future studies, the ONH may serve as a better reference point than the foveal center for expressing or depicting regional CT variations.

State of science: Choroidal thickness and systemic health

The choroid is a highly vascular structure; therefore, a wide range of systemic conditions can affect it. Conversely, choroid health may also give us insight into systemic health. With the emergence of optical coherence tomography, there has been a surge in the research on choroidal thickness and factors affecting it. Studies regarding the effect of systemic health on the choroid have largely been in the form of cross-sectional, prospective, and case studies. We offer a summary of recent findings on the topic.

Systematic Evaluation of Optical Coherence Tomography Angiography in Retinal Vein Occlusion.

PURPOSEnTo evaluate the clinical utility of optical coherence tomography angiography (OCTA) in patients with retinal vein occlusion (RVO), and to systematically compare OCTA images with changes seen on color fundus photography and fluorescein angiography (FA).nnnDESIGNnReliability analysis.nnnMETHODSnEighty-one eyes of 76 patients with a history of RVO (branch, central, or hemicentral), both acute and chronic, underwent OCTA and color fundus photography. In 29 eyes, data were compared to FA imaging. Comparative and multimodal analysis of the 3 imaging procedures were performed.nnnRESULTSnWe identified good agreement between FA and OCTA scans centered on the macula for capillary nonperfusion (intraclass correlation coefficient [ICC] 0.825 for the 3 × 3-mm scan and 0.891 for the 8 × 8-mm scan). Agreement for area of capillary changes (dilation, pruning, and telangiectasia) was also substantial (ICC 0.712 for the 3 × 3-mm scan and 0.787 for the 8 × 8-mm scan). For foveal avascular zone grading, agreement was good for the 3 × 3-mm scan (kappa = 1.000 for radius and kappa = 0.799 for outline) but poor for the 8 × 8-mm scan (kappa = 0.156 for radius and kappa = 0.600 for outline). The quality of the images obtained was an important issue for OCTA, as 15.1% of scans were nongradable, particularly in patients unable to maintain fixation.nnnCONCLUSIONSnOCTA is a quick, reliable, and noninvasive method to evaluate the area of capillary nonperfusion and foveal avascular zone morphology in patients with RVO. However, good fixation is a requirement for acquisition of good-quality images.

The Evaluation of Diabetic Macular Ischemia Using Optical Coherence Tomography Angiography

PURPOSEnThe purpose of this study was to compare optical coherence tomography (OCT) angiography to standard fluorescein angiography (FA) in the grading of diabetic macular ischemia.nnnMETHODSnIn our study, OCT angiography and traditional FA images were acquired from 24 diabetic patients. The level of diabetic macular ischemia in the superficial capillary plexus was graded with standard Early Treatment Diabetic Retinopathy Study (ETDRS) protocols and a comparison between conventional FA and OCT angiography was performed. The deep vascular plexus and choriocapillaris were also graded for macular ischemia. Additionally, flow indices were analyzed for all OCT angiography images.nnnRESULTSnWe identified moderate agreement between diabetic macular ischemia grades for conventional FA and OCT angiography (weighted κ of 0.53 and 0.41). In addition, the intergrader agreement for the superficial, deep, and choriocapillaris scores was substantial (weighted κ of 0.65, 0.61, and 0.65, respectively). Finally, the parafoveal flow indices were shown to have a statistically significant relationship with diabetic macular ischemia grades for the superficial capillary plexus (P = 0.04) and choriocapillaris (P = 0.036), with a trend toward significance for the deep capillary plexus (P = 0.13).nnnCONCLUSIONSnWe demonstrated moderate agreement between diabetic macular ischemia grading results for OCT angiography and conventional FA using standard ETDRS protocols. We also showed that OCT angiography images could be graded for diabetic macular ischemia with substantial intergrader agreement.

UK AMD EMR USERS GROUP REPORT V: benefits of initiating ranibizumab therapy for neovascular AMD in eyes with vision better than 6/12.

Background/aims To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy. Methods Multicentre national nAMD database study on patients treated 3–5u2005years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections. Results The study included 12u2005951 treatment-naive eyes of 11u2005135 patients receiving 92u2005976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values <0.001 for comparing differences between 6/12 and 6/12–6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values <0.001–0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12. Conclusions All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2u2005years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients’ funding.

Characterization of punctate inner choroidopathy using enhanced depth imaging optical coherence tomography.

PURPOSEnTo perform qualitative and quantitative analyses of retinal and choroidal morphology in patients with punctate inner choroidopathy (PIC) using enhanced depth imaging optical coherence tomography (EDI-OCT).nnnDESIGNnCross-sectional, consecutive series.nnnPARTICIPANTSnA total of 2242 patients attending 2 tertiary referral uveitis clinics at Moorfields Eye Hospital were screened; 46 patients with PIC diagnosis were identified, and 35 eyes (35 patients) had clinically inactive PIC had EDI-OCT images that met the inclusion criteria.nnnMETHODSnPunctate inner choroidopathy lesions were qualitatively assessed for retinal features, such as (1) focal elevation of the retinal pigment epithelium (RPE), (2) focal atrophy of the outer retina/RPE, and (3) presence of sub-RPE hyperreflective deposits and choroidal features: (a) presence of focal hyperreflective dots in the inner choroid and (b) focal thinning of the choroid adjacent to PIC lesions. Quantitative analyses of the retina, choroid, and choroidal sublayers were performed, and associations with clinical and demographic data were examined.nnnMAIN OUTCOME MEASURESnPrevalence of each lesion pattern and thickness of retinal and choroidal layers.nnnRESULTSnA total of 90 discrete PIC lesions were captured; 46.6% of PIC lesions consisted of focal atrophy of the outer retina and RPE; 34.4% consisted of sub-RPE hyperreflective deposits; and 18.8% consisted of localized RPE elevation with underlying hyporeflective space. Focal hyperreflective dots were seen in the inner choroid of 68.5% of patients, with 17.1% of eyes presenting focal choroidal thinning underlying PIC lesions. By excluding high myopes, patients with atypical PIC had reduced retinal thickness compared with patients with typical PIC (246.65±30.2 vs. 270.05±24.6 μm; P = 0.04), and greater disease duration was associated with decreases in retinal thickness (r = -0.53; P = 0.01). A significant correlation was observed between best-corrected visual acuity and foveal retinal thickness (r = -0.40; P = 0.03).nnnCONCLUSIONSnIn a large series of patients with clinically inactive PIC, one fifth of the lesions analyzed revealed RPE elevation with underlying hyporeflective space, described before as a sign of activity and suggesting subclinical inflammation. Retinal thickness seems to be associated with disease type and duration of disease in non-highly myopic eyes. Improved visualization of the inner choroid using EDI-OCT may allow noninvasive assessment of inflammatory status.

Automated analysis of retinal imaging using machine learning techniques for computer vision

There are almost two million people in the United Kingdom living with sight loss, including around 360,000 people who are registered as blind or partially sighted. Sight threatening diseases, such as diabetic retinopathy and age related macular degeneration have contributed to the 40% increase in outpatient attendances in the last decade but are amenable to early detection and monitoring. With early and appropriate intervention, blindness may be prevented in many cases. Ophthalmic imaging provides a way to diagnose and objectively assess the progression of a number of pathologies including neovascular (wet) age-related macular degeneration (wet AMD) and diabetic retinopathy. Two methods of imaging are commonly used: digital photographs of the fundus (the back of the eye) and Optical Coherence Tomography (OCT, a modality that uses light waves in a similar way to how ultrasound uses sound waves). Changes in population demographics and expectations and the changing pattern of chronic diseases creates a rising demand for such imaging. Meanwhile, interrogation of such images is time consuming, costly, and prone to human error. The application of novel analysis methods may provide a solution to these challenges. This research will focus on applying novel machine learning algorithms to automatic analysis of both digital fundus photographs and OCT in Moorfields Eye Hospital NHS Foundation Trust patients. Through analysis of the images used in ophthalmology, along with relevant clinical and demographic information, Google DeepMind Health will investigate the feasibility of automated grading of digital fundus photographs and OCT and provide novel quantitative measures for specific disease features and for monitoring the therapeutic success.

Structural changes of the choroid in sarcoid- and tuberculosis-related granulomatous uveitis

AimThe aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT).MethodsTwenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software.ResultsThe main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller’s large vessel and Sattler’s medium vessel layers) at the macula region. The ratio of Haller’s large vessel to Sattler’s medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72u2009μm)) compared with sarcoid uveitis (1.07 (=137.70/128.69u2009μm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1u2009μm (interquartile range (IQR)=147.0–253.4u2009μm) compared with those with VA <0.3 LogMAR (292.4u2009μm (IQR=240.1–347.6u2009μm)) at the total macula circle (P=0.004). At the foveal central subfield, the median choroidal thickness was 336.8u2009μm (IQR=272.3–375.4u2009μm) in active compared with 239.3u2009μm (IQR=195.3–330.9u2009μm) in quiescent disease (P=0.04).ConclusionA disproportionately enlarged Sattler’s layer may indicate a diagnosis of sarcoid-related uveitis, and choroidal thickening may be a feature of active granulomatous uveitis.

Vascular Changes in Eyes Treated with Dexamethasone Intravitreal Implant for Macular Edema after Retinal Vein Occlusion

OBJECTIVEnTo evaluate the angiographic findings in eyes from 2 clinical trials of the dexamethasone intravitreal implant (DEX implant) 0.7 mg in the treatment of macular edema (ME) after branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).nnnDESIGNnPost hoc analysis of pooled data from 2 identical phase 3 clinical trials.nnnPARTICIPANTSnPatients with vision loss as a result of ME (≥ 6 weeks duration) after BRVO or CRVO for whom angiographic data were available (n = 329 eyes).nnnMETHODSnFluorescein angiography (FA) results assessed by masked, certified graders using standardized grading protocols.nnnMAIN OUTCOME MEASURESnThe primary outcome measure in the parent studies was change from baseline in best-corrected visual acuity. Prospectively defined secondary outcomes included FA measurements (to assess macular capillary leakage, neovascularization, and nonperfusion) and optical coherence tomography results (to assess central retinal thickness [CRT]).nnnRESULTSnAt baseline, 42% of eyes in the DEX implant group and 38% of eyes in the sham group had unreadable assessments because of hemorrhage. At day 180, significantly fewer DEX implant-treated eyes (2%) than sham-treated eyes (9%) had unreadable assessments because of hemorrhage (P = 0.029). Among eyes with gradable assessments, the incidence of nonperfusion remained fairly steady from baseline to day 180. The proportion of eyes with active neovascularization increased from baseline to day 180 in the sham group, but stayed relatively constant in the DEX implant group (P = 0.026 for DEX vs. sham). The mean area of overall nonperfusion and the mean area of macular capillary nonperfusion increased from baseline to day 180 in both treatment groups (no statistically significant between-group difference). There was a statistically significant positive correlation between changes in macular leakage and changes in CRT in both the DEX implant group (r = 0.22; 95% confidence interval, 0.03-0.40; P = 0.023) and the sham group (r = 0.29; 95% confidence interval, 0.10-0.46; P = 0.003).nnnCONCLUSIONSnThis study demonstrated that the clinical improvements observed with the DEX implant were accompanied by significant improvements in vascular parameters and suggests that treatment with the DEX implant may be associated with some clinically significant improvements in angiographic findings, specifically active neovascularization.

Evaluation of Objective Vitritis Grading Method Using Optical Coherence Tomography: Influence of Phakic Status and Previous Vitrectomy.

PURPOSEnTo evaluate a proposed method for objective measurement of vitreous inflammation using a spectral-domain optical coherence tomography (SD OCT) device in a large cohort of uveitis eyes, including pseudophakic eyes and vitrectomized eyes.nnnDESIGNnRetrospective, observational cohort study.nnnMETHODSnOne hundred five uveitis eyes (105 patients) with different vitreous haze score grades according to standardized protocols and corresponding SD OCT images (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, California, USA) were included. Clinical data recorded included phakic status, previous vitreoretinal surgery, and anterior chamber (AC) cells and flare. SD OCT images were analyzed using custom software that provided absolute measurements of vitreous (VIT) and retinal pigment epithelium (RPE) signal intensities, which were compared to generate a relative optical density ratio with arbitrary units (VIT/RPE-relative intensity) and compared to VHS.nnnRESULTSnVIT/RPE-relative intensity showed a significant positive correlation with vitreous haze score (r = 0.535, P < .001) that remained significant after adjusting for factors governing media clarity, such as AC cells, AC flare, and phakic status (R(2)-adjusted = 0.424, P < .001). Significant differences were also observed between the different vitreous haze score groups (P < .001). Preliminary observation did not observe differences in VIT/RPE-relative intensity values between phakic and pseudophakic eyes (0.3522 vs 0.3577, P = .48) and between nonvitrectomized and vitrectomized eyes (0.3540 vs 0.3580, P = .52), overall and respectively for each vitreous haze score subgroup.nnnCONCLUSIONSnVIT/RPE-relative intensity values provide objective measurements of vitreous inflammation employing an SD OCT device. Phakic status and previous vitrectomy surgery do not appear to influence these values, although these preliminary findings need validation in future studies.