Praveen J. Patel

Repeatability of manual subfoveal choroidal thickness measurements in healthy subjects using the technique of enhanced depth imaging optical coherence tomography.

PURPOSE The aim of this study was to investigate the repeatability of manual measurements of choroidal thickness in healthy subjects imaged on spectral domain optical coherence tomography (OCT) using the enhanced depth imaging (EDI) technique. METHODS Fifty consecutive, healthy, young, adult volunteers with no known eye disease were enrolled prospectively. Two good-quality horizontal and vertical line scans through the fovea were obtained for each eye. Using the manual calipers provided by the software of the proprietary device, two experienced OCT readers measured the subfoveal choroidal thickness (SFCT) of the horizontal and vertical line scans for all eyes. The readers were masked to each others readings. Intraobserver, interobserver, and intrasession coefficients of repeatability (CRs) were calculated. RESULTS Mean (standard deviation [SD]) age of the study subjects was 38 (5) years (range, 30-49 years). Mean (SD) subfoveal choroidal thickness was 332 (90) μm (right eyes) and 332 (91) μm (left eyes). Intraobserver CR was approximately 23 (95% confidence interval [CI], 19-26) μm, whereas interobserver and intrasession CRs were greater at 32 (95% CI, 30-34) and 34 (95% CI, 32-36) μm, respectively. There was no significant difference in SFCT between all pairs of SFCT measurements except for the two intrasession vertical line scans. CONCLUSION A change of >32 μm was likely to exceed interobserver variability in SFCT. Future studies are required to estimate the repeatability of SFCT measurements in patients with chorioretinal pathology.

Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study.

Objectives To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration. Design Prospective, double masked, multicentre, randomised controlled trial. Setting Three ophthalmology centres in the United Kingdom. Participants 131 patients (mean age 81) with wet age related macular degeneration randomised 1:1 to intervention or control. Interventions Intravitreous bevacizumab (1.25 mg, three loading injections at six week intervals followed by further treatment if required at six week intervals) or standard treatment available at the start of the trial (photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration, or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration). Main outcome measures Primary outcome: proportion of patients gaining ≥15 letters of visual acuity at one year (54 weeks). Secondary outcomes: proportion of patients with stable vision and mean change in visual acuity. Results Of the 131 patients enrolled in the trial, five patients did not complete the study because of adverse events, loss to follow-up, or death. In the bevacizumab group, 21 (32%) patients gained 15 or more letters from baseline visual acuity compared with two (3%) in the standard care group (P<0.001); the estimated adjusted odds ratio was 18.1 (95% confidence interval 3.6 to 91.2) and the number needed to treat was 4 (3 to 6). In addition, the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment (91% (59) v 67% (44) in standard care group; P<0.001). Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the standard care group (P<0.001), and the initial improvement at week 18 (plus 6.6 letters) was sustained to week 54. Among 65 patients treated with bevacizumab, there were no cases of endophthalmitis or serious uveitis related to the intervention. All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over standard care. Conclusions Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to standard care (pegaptanib sodium, verteporfin, sham), with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 54 weeks. Trial registration number Current controlled trials ISRCTN83325075

Evaluation of Age-related Macular Degeneration With Optical Coherence Tomography

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.

Test-Retest Variability of Microperimetry Using the Nidek MP1 in Patients with Macular Disease

PURPOSE To determine the test-retest variability of the retinal sensitivity of the Nidek MP1 microperimeter in patients with macular disease. METHODS In this prospective study, 50 patients were enrolled with a range of macular diseases. One examiner performed two consecutive microperimetry tests for all patients using the same test strategy. Test-retest variability for mean sensitivity (MS), mean deviation (MD), point-wise sensitivity (PWS), local defect classification (LDC), average sensitivity for the central macula (CMS, 16 loci inside 10 degrees ), paracentral macular sensitivity (PMS, 52 loci in the 10 to 20 degrees ring), and dense scotoma size (DSS) were analyzed by calculating the 95% coefficients of repeatability or percentage agreement. RESULTS Mean (SD) age and visual acuity were 61 (15) years and 0.34 (0.32) logMAR, respectively. The mean difference in MS between tests 1 and 2 was +0.2 dB (SD, 0.9 dB; P = 0.127). The coefficients of repeatability for MS, MD, CMS, and PMS were 1.81, 2.56, 2.13, and 1.93 dB, respectively. The mean (SD) of coefficients of repeatability for PWS across all 68 loci was 5.56 (0.86) dB. Of all test loci in all patients 76% had perfect agreement in LDC, and 94% of patients had a change in DSS of four or fewer test loci. CONCLUSIONS Test-retest variability was lowest for MS and highest for PWS. However, MS does not provide spatial information. The authors recommend the use of CMS and PMS for monitoring macular function and consider a change of greater than 2.56 and 2.31 dB (the upper limit of the 95% confidence interval of their coefficients of repeatability), respectively, to exceed test-retest variability.

Topographic Variation and Interocular Symmetry of Macular Choroidal Thickness Using Enhanced Depth Imaging Optical Coherence Tomography

PURPOSE To report and analyze factors influencing topographical and interocular variations in choroidal thickness (CT) in a healthy adult population. METHODS One hundred eyes of 50 healthy subjects underwent visual acuity and axial length measurements and optical coherence tomography (OCT) with enhanced depth imaging (EDI). CTs at the fovea and at 3 mm nasal, temporal, superior, and inferior to the fovea were measured manually. Topographic variation, relative interocular differences in CT and predictors of CT were analyzed. The relationships between interocular differences in CT and differences in age and interocular axial length were explored. RESULTS The mean (SD) foveal CT in the right and left eyes were 334 (95) and 333 (90) μm, respectively. For foveal CT, there was a high correlation between the two eyes (r = 0.90) with a relative interocular 95% limits of agreement of -80 to +83, and a median (range) absolute difference of 21 (0.4-135). There was no significant variation in the relative and absolute interocular differences in CT. Axial length was the main predictor of CT for nasal and foveal CT. Symmetry in CT in the horizontal and vertical meridians was seen in eyes with axial length shorter than 23.50 mm (P < 0.05). CONCLUSIONS There was no significant relative interocular difference in CT. Axial length contributes to some of the variances in CT but has a significant influence on the CT profile. Although relative interocular difference is not significant, absolute interocular differences in CT may reach 85 μm.

Intersession Repeatability of Visual Acuity Scores in Age-Related Macular Degeneration

PURPOSE To describe the intersession repeatability of visual acuity measures obtained with Early Treatment of Diabetic Retinopathy Study (ETDRS) charts in patients with age-related macular degeneration. METHODS Visual acuity was measured in four sessions over 12 weeks using a standardized protocol with ETDRS charts in 107 nontreated eyes of 107 patients with age-related macular degeneration enrolled in an ongoing clinical trial. RESULTS Data from 90 patients were included in the analysis. The 95% coefficient of repeatability (CR) was 12 ETDRS letters and ranged from 9 letters for 29 eyes with small to intermediate drusen only to 17 letters for 25 eyes with late AMD (macular scars or geographic atrophy). Ten (11%) eyes had a 5-letter reduction or more in visual acuity at the week 1 visit compared with baseline. Excluding seven eyes with visual acuity measurements potentially affected by measurement-related factors (a change in testing distance between visits) the revised CR was 10 letters for the cohort (n = 83) and 11 letters for the late-AMD subgroup (n = 18). CONCLUSIONS Intersession ETDRS visual acuity measurements are subject to considerable variability in patients with AMD. The variability may be due to both measurement- and disease-related factors. The variable readings have implications for AMD clinical trial design and for the assessment and treatment of patients with neovascular AMD. Further work is needed to determine both the sources of variability in visual acuity measurements and the optimal change criterion for visual acuity measurements in this important group of patients.

Repeatability of stratus optical coherence tomography measures in neovascular age-related macular degeneration

PURPOSE To determine the repeatability of Stratus optical coherence tomography (OCT) measures of retinal thickness and volume in patients with neovascular age-related macular degeneration (nAMD) METHOD: Fifty-one eyes of 51 consecutive patients with nAMD underwent an OCT imaging session in which two fast macular thickness map (FMTM) protocol scans sets were acquired by a single experienced operator certified for clinical trials work. Coefficients of repeatability for each of nine Early Treatment of Diabetic Retinopathy Study (ETDRS)-like regions, foveolar center-point retinal thickness (CPT) and total macular volume (TMV), were calculated. Scans were analyzed retrospectively for errors in retinal boundary placement by two observers, with revised coefficients of repeatability calculated after excluding any scan sets with significant segmentation error. RESULTS The coefficient of repeatability for the central 1-mm macular subfield was 67 mum (23%) and was less than 75 mum for all macular subfields. There was much larger variability in the center-point thickness measure, with a coefficient of repeatability of 88 mum (32%) for the automated center-point thickness (ACPT). After excluding nine scan set pairs with significant segmentation error, the coefficient of repeatability for the central 1-mm macular subfield was reduced to 50 mum (19%). CONCLUSIONS OCT-derived retinal thickness measurements are subject to considerable measurement variability in patients with nAMD. Changes in central macular thickness of more than 50 mum may better reflect true clinical change in scan sets without significant segmentation error and may be used to guide the retreatment of patients with nAMD in clinical trials and clinical practice.

Segmentation error in stratus optical coherence tomography for neovascular age-related macular degeneration.

PURPOSE To describe the rate of automated segmentation error in Stratus optical coherence tomography (OCT) scans in consecutive patients with neovascular age-related macular degeneration (nAMD) receiving treatment and to investigate the effect of the segmentation error on automated retinal thickness measures and whether further imaging reduces the rate of segmentation error. METHODS A retrospective analysis of fast macular thickness map (FMTM) protocol OCT scans of 50 eyes of 50 consecutive patients with nAMD. Each line scan was analyzed for segmentation error with manual measurement of the center-point retinal thickness allowing calculation of the percentage error in automated thickness. OCT scanning was repeated to overcome segmentation error. RESULTS Segmentation error was detected in 45 (90%) of the 50 patients with 37 (74%) patients having an error affecting the central 1-mm subfield. Scan sets with a high central segmentation error score (two or more line scans affected of six) had a significantly greater error in automated center-point retinal thickness than scan sets with a low error score (20% compared with 3%, P < 0.000005). Central subfield segmentation error persisted in 30 (60%) patients despite repeat scanning. CONCLUSIONS There is a high rate of segmentation error in OCT scans of patients with nAMD who are undergoing treatment, leading to errors in automated central retinal thickness measurement. The authors recommend manual measurement of central macular thickness when two or more line scans are affected by segmentation error in the central 1-mm subfield. Repeated scanning reduced the rate of error but did not eliminate the problem.

Ranibizumab in myopic choroidal neovascularization: the 12-month results from the REPAIR study

pathophysiology in LHON. In this study, we reported that ganglion cell analysis could precisely detect the loss of retinal ganglion cell in a time-dependent manner during early phase of LHON when RNFL thickness had not decreased yet. We also raise the possibility that there might be many more patients>60 years of age with visual loss owing to LHON than we have supposed previously. It may be worth investigating mtDNA point mutations regardless of age if a patient presents with unknown visual acuity loss with central scotoma.

A Comparison of Macular Translocation with Patch Graft in Neovascular Age-Related Macular Degeneration

PURPOSE To compare the long-term outcomes of macular translocation (MT) and autologous RPE-choroid patch graft (PG) in patients with neovascular age-related macular degeneration (AMD). METHODS This is a retrospective review of the first 12 patients who underwent MT and the first 12 patients who underwent PG. Visual acuity (VA), contrast sensitivity (CS), clinical findings, and complications were recorded. Microperimetry and fundus imaging were reviewed. Outcome measures were the change in VA and CS over 3 years in each group and rates of complication. Microperimetry and fixation in three best cases from each group were described. RESULTS The two groups were matched for age and VA. Median follow-up durations were 41 (MT) and 38 (PG) months. Median VA (logMAR) was maintained in the MT group: 0.90 at baseline and 0.69 at 3 years (P=0.09) whereas in the PG group, median VA declined from 0.87 to 1.38 at 3 years (P<0.001). Both surgical modalities had high rates of detachment and macular edema. Although more extensive RPE damage occurred in PG, the graft resisted growth of recurrent choroidal neovascularization toward the fovea. Near normal VA was achievable by each technique but macular sensitivity and fixation stability were superior in the MT group. CONCLUSIONS In the present cohort, MT maintained VA for 3 years but PG did not. This outcome may be related to the differences in surgical approach, source of RPE, and choroidal perfusion. The authors recommend MT in preference to PG for treatment of patients with the second eye affected by neovascular AMD unsuitable for other treatment.