Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea

PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.     

Comparison of penetration depth in choroidal imaging using swept source vs spectral domain optical coherence tomography

Purpose

To compare signal penetration depth and deep structure-visualization of swept source (SS) and spectral domain (SD)-optical coherence tomography (OCT) with and without enhanced depth imaging (EDI) and B-scan averaging modes.

Methods

Volume scans were obtained from 20 eyes of healthy volunteers by DRI OCT-1, Spectralis using EDI and B-scan averaging, and Cirrus HD-OCT. The signal penetration depth was measured as the distance between the retinal pigment epithelium and the deepest visible anatomical structure at the foveal center. Visibility and contrast of the choroidoscleral junction and of vascular details within the choroid were assessed across the entire volume using an ordinal scoring scale. Outcome measures were compared using paired t-test and rank-sum test.

Results

The mean signal penetration depth was 498±114 μm for Spectralis, 491±85 μm for DRI OCT-1, and 123±65 μm for Cirrus; P=0.9708 Spectralis vs DRI OCT-1, P<0.0001 Spectralis vs Cirrus, and P<0.0001 DRI OCT-1 vs Cirrus. Mean ranks for visibility and contrast of the choroidoscleral junction were 3.83 for Spectralis, 3.98 for DRI OCT-1, and 2.00 for Cirrus; and 3.45 for Spectralis, 2.93 for DRI OCT-1, and 1.58 for Cirrus. Mean ranks for visibility and contrast of vascular details were 3.73 (Spectralis), 3.70 (DRI OCT-1), and 2.23 (Cirrus); and 3.53 (Spectralis), 2.05 (DRI OCT-1), and 1.98 (Cirrus).

Conclusion

Signal penetration depths are similar for SS-OCT and SD-OCT using EDI and frame averaging, and statistically significantly lower without EDI/averaging. Both SD-OCT using EDI/frame averaging and SS-OCT offer excellent visualization capabilities for volumetric imaging of the choroidoscleral interface.     

Biometrics,Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration

PurposeBasal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).MethodsDonor eyes were classified as early to intermediate AMD (n = 25) and age-matched controls (n = 54). In high-resolution histology, we assessed BLinD/soft drusen thickness at 836 and 1716 locations in AMD and control eyes, respectively. BLinD volume was estimated using solid geometry in donor eyes, one clinically characterized.ResultsBLinD, drusen, type 1 MNV, and fluid occupy the sub-RPE-basal laminar space. BLinD volume in a 3-mm diameter circle may be as much as 0.0315 mm³. Osmophilic lipid was more concentrated in BLinD/drusen than SDD. In the fovea, BLinD/drusen was prevalent in AMD eyes; pre-BLinD was prevalent in control eyes. SDD was low in the fovea and high in perifovea, especially in AMD eyes.ConclusionsAlthough invisible, BLinD may presage type 1 MNV. BLinD volume approaches the criterion OCT drusen volume of 0.03 mm³ for AMD progression risk. BLinD culminates years of subfoveal lipid accumulation. SDD is detected relatively late in life, with currently unknown precursors. Deposit topography suggests one outer retinal lipid recycling system serving specialized cone and rod physiology, and its dysregulation in AMD is due to impaired transfer to the circulation.     

Effect of OCT volume scan density on thickness measurements in diabetic macular edema

Purpose

To evaluate the impact of reducing B-scan frame-sampling density on retinal thickness measurements using spectral domain optical coherence tomography (SD-OCT) in eyes with diabetic macular edema (DME).

Methods

We retrospectively collected OCT data for 64 eyes of 43 patients undergoing imaging for DME using the Cirrus HD-OCT 512 × 128 macular cube protocol. For each case, raw OCT data were imported into the 3D-OCTOR software, and retinal thickness maps were generated using all 128 B-scans and for lower densities of B-scans ranging from every other scan to only four scans (every 30-s B-scan). Maps were generated before and after manual correction of retinal boundary segmentation errors. The foveal central subfield (FCS) and total macular volume (TMV) values were used to compare thickness maps of varying densities.

Results

The mean difference in FCS retinal thickness and TMV increased as the B-scan density was reduced, particularly when the density was reduced to fewer than 16 B-scans over 6 mm. At a density of 16 B-scans, the mean absolute difference in FCS thickness was 2.43 μm (0.79%), with a maximum of 10.1 μm (4.09%). At this density, the mean difference in TMV was 0.012 mm³ (0.13%), with a maximum difference of 0.04 mm³ (0.47%). Manual correction of OCT segmentation errors resulted in a difference in FCS thickness of ≥10 μm in only 12.5% of cases, with a maximum difference of 115.7 μm.

Conclusion

A minimum of 16 equally spaced B-scans appear necessary to generate retinal thickness measurements similar to those produced using all 128 B-scans in eyes with DME. Manual correction of segmentation errors appeared to have a clinically meaningful effect in a small minority of cases. These results may have implications for the design of SD-OCT imaging and grading protocols in clinical trials of DME, particularly when using multiple SD-OCT instruments that acquire varying numbers of B-scans.     

Grado de concordancia y diferencias entre valores maculares en niños mediante dos tipos de tomografía de coherencia óptica espectral

ObjectiveTo determine the degree of agreement and differences between macular parameters according to sex, age, laterality, ethnicity and type of optical coherence tomography (OCT) in paediatric patients.Materials and methodsProspective, transversal, and comparative study. OCT Spectralis and OCT Cirrus were used to obtain the macular values of both eyes in 100 patients between 5 and 15 years without ocular pathology. Due to the similarity between the values of both eyes, in the final sample we only considered the right eyes (OD) (n = 100).ResultsThe average central macular thickness (CMT) was 244.2 μm with Cirrus and 261.7 μm with Spectralis. The degree of agreement for the GMC was moderate (intraclass correlation coefficient: 0.66) and from low to very low in the other quadrants. The GMC values of both systems were significantly higher in men than in women (P < .05). The macular retinal nerve fibre layer (mRNC), ganglion cell layer (GCC), the inner plexiform layer (IPLC), and the inner nuclear layer (INFL) had significantly higher values in men than in women (P < .01). There were no statistically significant differences in the GMC by age and laterality, however it was significantly higher in ethnic European children than in ethnic Latin American children; Cirrus (P = .042) and Spectralis (P = .033).ConclusionsMacular parameters obtained by OCT Spectralis and OCT Cirrus should not be interchangeable in pediatric patients.     

Foveal Thickness between Stratus and Spectralis Optical Coherence Tomography in Retinal Diseases

Purpose

To compare the foveal thickness (FT) parameters measured by Stratus optical coherence tomography (OCT) and Spectralis OCT in various retinal diseases and to construct conversion formulas between the two types of OCT devices.

Methods

We examined 366 consecutive patients (475 eyes) with retinal diseases and 13 normal controls (13 eyes). The patients were categorized into eight retinal disease groups. The mean amount and distribution of foveal thickness differences (FTD) measured by Stratus and Spectralis OCT were determined, and conversion formulas were constructed for Stratus OCT FT from Spectralis OCT FT for each retinal disease group.

Results

Among retinal diseases, the mean FTD was significantly larger in exudative age-related macular degeneration (AMD) patients (mean ± SD, 94.0 ± 55.0 µm) compared to normal subjects (66.2 ± 11.7 µm; p < 0.0001). The proportion of eyes with a mean FTD outside 1.96 standard deviations of normal subject FTD was greatest in the exudative AMD (50.0%) group and smallest in the macular hole (18.2%) group. The predicted FTs obtained through the conversion formulas showed lower variance than the actual FTD values, especially in the exudative AMD group. The prediction line for exudative AMD deviated most from that of normal subjects.

Conclusions

FTD shows diverse values and variances among various retinal diseases, especially in exudative AMD, which indicates that Stratus OCT FT cannot be predicted from Spectralis OCT FT by FTD value alone. We constructed statistically significant conversion formulas, which provided more reliable methods to predict Stratus OCT-measured FT from Spectralis OCT measurements for different retinal disease groups.     

Segmentation error and macular thickness measurements obtained with spectral-domain optical coherence tomography devices in neovascular age-related macular degeneration

Purpose:

To evaluate frequency and severity of segmentation errors of two spectral-domain optical coherence tomography (SD-OCT) devices and error effect on central macular thickness (CMT) measurements.

Materials and Methods:

Twenty-seven eyes of 25 patients with neovascular age-related macular degeneration, examined using the Cirrus HD-OCT and Spectralis HRA + OCT, were retrospectively reviewed. Macular cube 512 × 128 and 5-line raster scans were performed with the Cirrus and 512 × 25 volume scans with the Spectralis. Frequency and severity of segmentation errors were compared between scans.

Results:

Segmentation error frequency was 47.4% (baseline), 40.7% (1 month), 40.7% (2 months), and 48.1% (6 months) for the Cirrus, and 59.3%, 62.2%, 57.8%, and 63.7%, respectively, for the Spectralis, differing significantly between devices at all examinations (P < 0.05), except at baseline. Average error score was 1.21 ± 1.65 (baseline), 0.79 ± 1.18 (1 month), 0.74 ± 1.12 (2 months), and 0.96 ± 1.11 (6 months) for the Cirrus, and 1.73 ± 1.50, 1.54 ± 1.35, 1.38 ± 1.40, and 1.49 ± 1.30, respectively, for the Spectralis, differing significantly at 1 month and 2 months (P < 0.02). Automated and manual CMT measurements by the Spectralis were larger than those by the Cirrus.

Conclusions:

The Cirrus HD-OCT had a lower frequency and severity of segmentation error than the Spectralis HRA + OCT. SD-OCT error should be considered when evaluating retinal thickness.     

Comparison of retinal thickness values and segmentation performance of different OCT devices in acute branch retinal vein occlusion

Purpose

To compare retinal thickness (RT) measurement and segmentation performance of time domain (TD, Stratus) and spectral domain (SD) optical coherence tomography (OCT) devices (Cirrus, Spectralis) for imaging macular oedema (ME) secondary to branch retinal vein occlusion (BRVO).

Methods

In this study, 20 eyes of 20 consecutive patients with acute BRVO were included. A total of 18 unaffected fellow eyes served as control group. RT measurement was analysed in the five inner fields of the early-treatment diabetic retinopathy grid, and proportional segmentation errors were evaluated.

Results

Central millimetre thickness (CMT) showed a mean difference of −64, −74, and −18 μm (P<0.001) in the control group and −31 μm (P=0.107), −92 μm (P<0.001), and −105 μm (P=0.016) in the BRVO group, between Stratus and Cirrus, between Stratus and Spectralis, and between Cirrus and Spectralis, respectively. Mean RT showed the highest variability between different devices in the area most intensively affected by BRVO-related ME. In eyes with BRVO, 14.6% of Spectralis, 20% of Stratus, and 36.6% of Cirrus scans demonstrated moderate and severe segmentation errors.

Conclusion

RT measurement in eyes with BRVO, by TD and SD OCT, is compromised by a significant rate of segmentation errors. Deviations are most pronounced in the areas most severely affected by ME.     

Grado de concordancia y diferencias entre los valores de capa de fibras nerviosas de la retina peripapilar en niños mediante dos tipos de tomografía de coherencia óptica espectral

ObjectiveTo assess absolute agreement and differences in peripapillary retinal nerve fiber layer (pRNFL) values according to sex, age, laterality, origin and optical coherence tomography (OCT) type in normal pediatric patients undergoing OCT scans using both Cirrus and Spectralis.Material and methodsProspective, cross-sectional, and comparative study. We used Spectralis OCT and Cirrus OCT to measure optic disc values of both eyes in one hundred pediatric patients (age 5 to 15 years), with no previous ocular pathology or systemic disease that could affect the eye. Due to the similarity between eyes, only right eyes were considered (n = 100).ResultsThe average peripapillary retinal nerve fiber layer (pRNFL) values were 99.6 μm with Cirrus and 106.7 μm with the Spectralis system. The four quadrants followed the ISNT rule (inferior-superior-nasal-temporal). The average pRNFL measures correlated negatively with the AL (P < .01) in both OCTs, and the degree of agreement between OCTs for pRNFL and inferior RNFL was moderate (CCI: 0.67 and 0.61, respectively), and low in the rest of the sectors. The average pRNFL values of both OCTs were higher in women than in men (P > .05) and there were also no statistical differences in the pRNFL according to age or laterality (P > .05). All RNFL values were significantly different between both types of OCTs (P < .05) and average pRNFL values were significantly thicker (P < .05) in Latin American than in European children in both eyes.ConclusionsWe suggest that the respective peripapillary RNFL values obtained using these two OCTs should not be considered interchangeable in pediatric patients.     

A comparison of false positives in retinal nerve fiber layer,optic nerve head and macular ganglion cell-inner plexiform layer from two spectral-domain optical coherence tomography devices

Background

The incidence of false positive (FP) results of optic coherence tomography (OCT) retinal nerve fiber layer (RNFL) color code in healthy subjects can be very high with Cirrus OCT. Recent evidence has shown that OCT parameters derived from macular ganglion cell-inner plexiform layer (GCIPL) have excellent ability to discriminate between normal eyes and eyes with early glaucoma.

Methods

This was a prospective, cross-sectional study. One hundred eyes from 50 healthy volunteers underwent circumpapillary scanning by Cirrus and Spectralis OCT and macular scanning using Cirrus OCT. FP rates for each of the OCT parameters, using predefined criteria for an abnormal test were calculated. Comparative analysis was performed using the McNemar test. A generalized estimating equations model (GEE) was used to compare demographic and clinical factors between the eyes with normal findings and eyes with abnormal results.

Results

The overall RNFL color-code FP rate was significantly higher for Cirrus (39 %) than for Spectralis (18 %) (P?=?0.000). The Spectralis RNFL FP rate showed no significant difference when compared to the FP rate by Cirrus GCIPL (13 %) and ONH (11 %) analysis. Axial length, mean spherical equivalent, presence of peripapillary atrophy, and tilted disc were significantly related to the RNFL FP occurrence displayed by both devices.

Conclusions

Spectralis might be more specific than Cirrus when evaluating the RNFL thickness for Caucasians and moderate myopic population. GCIPL and ONH analysis might be more useful than RNFL thickness to evaluate this population using Cirrus OCT.     

Choroidal vascularity index as an indicator of vascular status of choroid,in eyes with nanophthalmos

PurposeTo investigate choroidal vascular index (CVI) in eyes with nanophthalmos (NO) with the use of optical coherence tomography (OCT).MethodsMacular enhanced depth imaging OCT scans of 25 eyes of 25 patients with NO and age–gender-matched 25 eyes of 25 control subjects were analysed. Images were binarized using the ImageJ software, and total choroid area (TCA), luminal area (LA) and stromal area (SA) were acquired. The main outcome measure was CVI, defined as the ratio of LA to TCA.ResultsTwenty-five eyes of 25 patients with NO and age–gender-matched control subjects were enrolled. The mean TCA, SA and LA were found to be significantly higher in patients with NO (2.51 ± 0.44 vs. 1.91 ± 0.35 mm², P < 0.001; 0.86 ± 0.17 vs. 0.63 ± 0.13 mm², P < 0.001; and 1.65 ± 0.29 vs. 1.27 ± 0.23 mm², P < 0.000, respectively). On the contrary, CVI did not significantly differ between the two groups (65.72, 67.68, P = 0.099).ConclusionAs a novel OCT-based marker, CVI could be used to assess vascular status of the choroid in eyes with NO and can provide better understanding of the pathogenesis of this disease.Subject terms: Eye abnormalities, Scleral diseases, Predictive markers, Hereditary eye disease, Uveal diseases     

Evaluation of posterior and total corneal astigmatism with colour-LED topography

PurposeTo characterise the posterior and total corneal astigmatism using colour point-source light-emitting diodes (LED) topography.MethodsIn a prospective case series 400 eyes from 400 patients were evaluated by colour-LED topography. Only eyes with normal topographies were considered. The following parameters were studied: magnitude and distribution of SimK and posterior corneal astigmatism, correlation between SimK and posterior corneal astigmatism, and differences in magnitude and axis between total and anterior corneal astigmatism.ResultsThe mean SimK corneal astigmatism was 1.21 ± 0.94 D. The mean posterior corneal astigmatism was 0.37 ± 0.24 D. Posterior astigmatism was vertically oriented in 68% of eyes. Twenty-two percent of eyes showed a posterior corneal astigmatism ≥ 0.50 D. The correlation coefficients between SimK and posterior corneal astigmatism were: r² = 0.066; p = 0.371 in WTR eyes, r² = 0.112; p = 0.173 in ATR eyes and r² = −0.019; p = 0.879 in oblique eyes. A difference between SimK and total corneal astigmatism ≥ 0.50 D was found in 7% of eyes. A difference in axis between SimK and total corneal astigmatism ≥ 10° was found in 24% of eyes.ConclusionsThe percentage of eyes with posterior corneal astigmatism ≥ 0.50 D and the differences between anterior and total corneal astigmatism were higher than those previously reported in the literature. Therefore, this study supports the consideration of total corneal astigmatism magnitude and axis is mandatory for a precise surgical correction of astigmatism.Subject terms: Medical research, Health care     

Inter-observer agreement for spectral- and time-domain optical coherence tomography image grading: a prospective study

The purpose of this study was to compare inter-observer agreement of Stratus? OCT versus Spectralis? OCT image grading in patients with neovascular age-related macular degeneration (AMD). Thirty eyes with neovascular AMD were examined with Stratus? OCT and Spectralis? OCT. Four different scan protocols were used for imaging. Three observers graded the images for the presence of various pathologies. Inter-observer agreement between OCT models was assessed by calculating intra-class correlation coefficients (ICC). In Stratus? OCT highest interobserver agreement was found for subretinal fluid (ICC: 0.79), and in Spectralis? OCT for intraretinal cysts (IRC) (ICC: 0.93). Spectralis? OCT showed superior interobserver agreement for IRC and epiretinal membranes (ERM) (ICC_Stratus?: for IRC 0.61; for ERM 0.56; ICC_Spectralis?: for IRC 0.93; for ERM 0.84). Increased image resolution of Spectralis? OCT did improve the inter-observer agreement for grading intraretinal cysts and epiretinal membranes but not for other retinal changes.     

Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer's disease

Background

To evaluate and compare the ability of two Fourier-domain optical coherence tomography (OCT) devices to detect retinal and retinal nerve fibre layer (RNFL) atrophy in patients with Alzheimer''s disease (AD) compared with healthy subjects; to test the intra-session reliability of two OCT devices in AD patients and healthy subjects.

Methods

AD patients (n=75) and age-matched healthy subjects (n=75) underwent three Macular Cube 200 × 200 protocols using the Cirrus and Spectralis OCT devices and three 360° circular scans centred on the optic disc using the Cirrus OCT device, the classic glaucoma application, and the new Nsite Axonal Analytics application of the Spectralis OCT instrument. Differences between healthy and AD eyes were compared, and measurements provided by each OCT protocol were compared. Reliability was measured using intraclass correlation coefficients and coefficients of variation. Correlations between OCT measurements and disease duration and severity were also analysed.

Results

Retinal thinning was observed in AD eyes in all areas except the fovea using both OCT devices. RNFL atrophy was detected in AD eyes with all three protocols, but the Nsite Axonal application was the most sensitive. Measurements by the two OCT devices were correlated, but differed significantly. Reliability was good using all protocols, but better with the glaucoma application of Spectralis. Mean RNFL thickness provided by the Nsite Axonal application correlated with disease duration.

Conclusions

Fourier-domain OCT is a valid and reliable technique for detecting subclinical RNFL and retinal atrophy in AD, especially using the Nsite Axonal application. RNFL thickness decreased with disease duration.     

Prevalence and risk factors for age-related macular degeneration in the elderly Chinese population in south-western Taiwan: the Puzih eye study

Aim

This study aimed to ascertain the prevalence of and the risk factors associated with early and late age-related macular degeneration (AMD) among Chinese individuals aged ≥65 years residing in Puzih, Taiwan.

Methods

This population-based cross-sectional study graded digital colour photographs of the ocular fundus of 673 individuals using the Wisconsin Age-Related Maculopathy Grading System. We compared the characteristics of individuals with early and late AMD using χ²-analyses and described risk factors for early and late AMD using odds ratios and 95% confidence intervals.

Results

Individuals with late AMD were significantly older and more likely to have hypertension. Further, their sunlight exposure time was longer than that of those with early AMD, only drusen, or no AMD lesions (P<0.01). A history of hyperlipidaemia for >10 years was a significant risk factor for early AMD, while old age, hypertension for >10 years, and exposure to sunlight for >8 h per day were associated with late AMD.

Conclusions

The prevalence rate of early AMD in the present study was 15.0%, which is similar to that reported for Caucasians and Japanese included in the European Eye Study and the Hisayama Study, respectively. The late AMD prevalence rate of 7.3% found among our study participants was comparable to that reported by the Greenland Inuit Eye Study and Reykjavik Study, but considerably lower than that reported for Caucasians, indicating that late AMD might be less prevalent among Asians than Caucasians.     

Clinical features of microvasculature in subzones of parapapillary atrophy in myopic eyes: an OCT-angiography study

PurposeTo investigate the microvasculature in subzones of parapapillary atrophy (PPA) and their associated factors in healthy myopic eyes using optical coherence tomography (OCT) angiography.MethodsThe cross-sectional study included 55 healthy myopic eyes with PPA. The superficial radial peripapillary capillary (RPC) and choroidal microvascular densities were delineated and measured in alpha, beta, and gamma zone PPA using OCT angiography, respectively. The structural parameters including the width and area in each subzone and corresponding retinal nerve fiber layer thickness were further measured. Statistical analysis was performed to explore the relationship between the vascular and structural parameters.ResultsThe mean age and mean axial length of the participants were 27.55 ± 5.72 years and 25.19 ± 1.08 mm. Among alpha, beta, and gamma zone PPA, the beta zone showed the lowest RPC density, which was negatively correlated with the area and width of beta zone (P < 0.05). The gamma zone showed the highest RPC density, which was positively correlated with the retinal nerve fiber layer thickness of gamma zone (P < 0.01). Compared with alpha zone, both gamma and beta zones showed marked decrease of choriocapillaris. The beta zone showed a lower choroidal microvascular density than that of gamma zone (P < 0.01). Choroidal microvascular density in beta and gamma zones were negatively correlated with the width of beta zone and gamma zone, respectively (P < 0.01).ConclusionsTopographic differences on superficial RPC and choroidal microvasculature were found among the subzones of PPA. A microcirculatory deficiency in beta zone PPA may exist in myopic eyes.Subject terms: Refractive errors, Refractive errors, Eye manifestations, Eye manifestations     

Visual and anatomical outcomes following intravitreal aflibercept in eyes with recalcitrant neovascular age-related macular degeneration: 12-month results

Purpose

To describe the efficacy of intravitreal aflibercept on 12-month visual and anatomical outcomes in patients with neovascular age-related macular degeneration (AMD) recalcitrant to prior monthly intravitreal bevacizumab or ranibizumab.

Methods

Non-comparative case series of 21 eyes of 21 AMD patients with evidence of persistent exudation (intraretinal fluid/cysts, or subretinal fluid (SRF), or both) on spectral domain OCT despite ≥6 prior intravitreal 0.5 mg ranibizumab or 1.25 mg bevacizumab (mean 29.8±17.1 injections) over 31.6±17.4 months who were transitioned to aflibercept.

Results

At baseline, best-corrected visual acuity (BCVA) was 0.42±0.28 logarithm of minimum-angle of resolution (logMAR), central foveal thickness (CFT) was 329.38±102.67 μm and macular volume (MV) was 7.71±1.32 mm³. After 12 months of aflibercept (mean 10.2±1.2 injections), BCVA was 0.40±0.28 logMAR (P=0.5), CFT decreased to 292.71±91.35 μm (P=0.038) and MV improved to 7.33±1.27 mm³ (P=0.003). In a subset of 15 eyes with a persistent fibrovascular or serous pigment epithelial detachment (PED), mean baseline PED greatest basal diameter (GBD) was 2350.9±1067.6 μm and mean maximal height (MH) was 288.7±175.9 μm. At 12 months, GBD improved to 1896.3±782.3 μm (P=0.028), while MH decreased to 248.27±146.2 μm (P=0.002).

Conclusion

In patients with recalcitrant AMD, aflibercept led to anatomic improvement at 12 months, reduction in proportion of eyes with SRF and reduction in PED, while preserving visual acuity.     

Retinal nerve fiber layer and optic disc measurements by spectral domain OCT: normative values and associations in young adults

Purpose

To determine normative values and associations of retinal nerve fiber layer (RNFL) and optic disc parameters in normal eyes measured by spectral domain optical coherence tomography (OCT).

Methods

In a population-based setting, 1521 young adults were examined as part of the Sydney Adolescent Vascular and Eye Study (SAVES). Their mean age was 17.3±0.6 years. RNFL and optic disc parameter measurements were made using Cirrus HD-OCT 4000.

Results

The average RNFL was found to be 99.4±9.6 μm. RNFL thickness was least for the temporal quadrant (69.9±11.2 μm), followed by the nasal (74.3±12.8 μm), superior (124.7±15.7 μm) and inferior (128.8±17.1 μm) quadrants. The mean disc area in this population was 1.98±0.38 mm² with a mean rim area of 1.50±0.30 mm² and a mean cup/disc ratio of 0.44±0.18. Multivariate-adjusted RNFL thickness was marginally greater in East Asian than in white participants (100.1 μm vs 99.5 μm; P=0.0005). The RNFL was thinner with greater axial length (P<0.0001), less positive spherical equivalent refractions (P<0.0001), smaller disc area and rim area (P<0.0001).

Conclusion

This study documents normative values for the RNFL and optic disc measured using Cirrus HD-OCT in young adults. The values and associations reported in this study can inform clinicians on the normal variation in RNFL and optic disc parameters.     

Bilateral involvement by age related maculopathy lesions in a population

AIMS—To describe the influences of age and sex on the frequency of bilateral age related macular degeneration (AMD) and age related maculopathy (ARM) lesions.
METHODS—The Blue Mountains Eye Study examined 3654 older Australians, 82% of permanent residents living in an area west of Sydney. Stereo macular photographs were graded for AMD (neovascular maculopathy and geographic atrophy) and early ARM lesions (soft drusen, reticular drusen, hyperpigmentation, and hypopigmentation).
RESULTS—Among 230 gradable cases of AMD or early ARM, 183 (80%) were bilateral. For AMD, 39/69 cases (57%) were bilateral, while for early ARM, 123/161 cases (77%) had signs in both eyes. Of the individual lesions, reticular drusen (91%) and indistinct soft drusen (79%) were most frequently present in both eyes. Geographic atrophy was bilateral in 56%, neovascular AMD in 40%, and distinct soft drusen in 47%, while hyperpigmentation was bilateral in 38% and hypopigmentation in only 28% of cases. A consistent age related increase in bilateral distribution was observed for most lesions. After adjusting for effects of age, current smoking, and AMD family history AMD and ARM component lesions, except for soft drusen, were more frequently bilateral in women. This sex difference was significant only for neovascular AMD, odds ratio 7.7 (95% confidence intervals 1.3-46.7). An AMD family history was more frequently reported in cases with bilateral involvement.
CONCLUSIONS—This study has documented differences in the age related bilaterality of individual ARM components with higher bilateral rates for reticular or indistinct soft drusen compared with other lesions. The increased bilaterality of most ARM lesions among women is likely to contribute to the increased age adjusted risk of AMD blindness found in women.

Keywords: age related maculopathy; age related macular degeneration; drusen     

Prospective deep phenotyping of choroideremia patients using multimodal structure-function approaches

ObjectiveTo investigate the retinal changes in choroideremia (CHM) patients to determine correlations between age, structure and function.Subjects/MethodsTwenty-six eyes from 13 male CHM patients were included in this prospective longitudinal study. Participants were divided into <50-year (n = 8) and ≥50-year (n = 5) old groups. Patients were seen at baseline, 6-month, and 1-year visits. Optical coherence tomography (OCT), OCT angiography, and fundus autofluorescence were performed to measure central foveal (CFT) and subfoveal choroidal thickness (SCT), as well as areas of preserved choriocapillaris (CC), ellipsoid zone (EZ), and autofluorescence (PAF). Patients also underwent functional investigations including visual acuity (VA), contrast sensitivity (CS), colour testing, microperimetry, dark adaptometry, and handheld electroretinogram (ERG). Vision-related quality-of-life was assessed by using the NEI-VFQ-25 questionnaire.ResultsOver the 1-year follow-up period, progressive loss was detected in SCT, EZ, CC, PAF, and CFT. Those ≥50-years exhibited more structural and functional defects with SCT, EZ, CC, and PAF showing strong correlation with patient age (rho ≤ −0.47, p ≤ 0.02). CS and VA did not change over the year, but CS was significantly correlated with age (rho = −0.63, p = 0.001). Delayed to unmeasurable dark adaptation, decreased colour discrimination and no detectable ERG activity were observed in all patients. Minimal functional deterioration was observed over one year with a general trend of slower progression in the ≥50-years group.ConclusionsQuantitative structural parameters including SCT, CC, EZ, and PAF are most useful for disease monitoring in CHM. Extended follow-up studies are required to determine longitudinal functional changes.Subject terms: Hereditary eye disease, Prognostic markers