Identification of microvascular and morphological alterations in eyes with central retinal non-perfusion.

PURPOSE: To evaluate the characteristics and morphological alterations in central retinal ischemia caused by diabetic retinopathy (DR) or retinal vein occlusion (RVO) as seen in optical coherence tomography angiography (OCTA) and their relationship to visual acuity. METHODS: Swept-source optical coherence tomography (SSOCT) and OCTA (Topcon, Triton) data of patients with central involving retinal ischemia were analyzed in this cross-sectional study. The following parameters were evaluated: vessel parameters, foveal avascular zone (FAZ), intraretinal cysts (IRC), microaneurysms (MA), vascular collaterals in the superficial (SCP) and deep plexuses (DCP), hyperreflective foci (HRF), epiretinal membrane (ERM), external limiting membrane (ELM) and ellipsoid zone (EZ) disruption, as well as the disorganization of retinal inner layers (DRIL). Best-corrected visual acuity (BCVA), age, gender, disease duration and ocular history were also recorded. RESULTS: 44 eyes of 44 patients (22 with RVO, 22 with DR) were analyzed. The mean age was 60.55 ± 11.38 years and mean BCVA 0.86 ± 0.36 (Snellen, 6m). No significant difference was found between DR subgroups (non proliferative vs. proliferative). Between RVO subgroups (CRVO vs. BRVO) a significant difference was found in term of collateral vessel of the DCP (p = 0.014). A pooled DR and RVO group were created and compared. Significantly more MAs (p = 0.007) and ERM (p = 0.007) were found in the DR group. Statistically significant negative correlation was demonstrated between FAZ and BCVA (p = 0.45) when analyzing all patients with retinal ischemia. CONCLUSION: This study has shown that the best predictor of visual outcome in center involved ischemic diseases is the size of FAZ. Besides the presence of MAs and ERM, all other OCT and OCTA parameters were present in a similar extent in DR and RVO group despite the completely different disease origins. Our results suggest that as soon as retinal ischemia in the macular region is present, it has a similar appearance and visual outcome independently of the underlying disease.

Semi-automated quantification of geographic atrophy with blue-light autofluorescence and spectral-domain optical coherence tomography: a comparison between the region finder and the advanced retinal pigment epithelium tool in the clinical setting.

PURPOSE: To compare inter- and intraobserver reliability and intermodality agreement on quantification of geographic atrophy, using two routinely available quantification tools, based on blue-light fundus autofluorescence (BAF) and spectral-domain optical coherence tomography (SD-OCT). METHODS: Quantifications of atrophic lesions within the central 5 mm of 30 eyes from 30 patients (mean age: 76.1 years) were independently performed by two clinicians on BAF images using the region finder (RF; Heidelberg Engineering) and on SD-OCT using the advanced retinal pigment epithelium tool (ARPET; Carl Zeiss Meditec) at baseline and follow-up (mean interval: 336 days). Inter- and intraobserver reliability was determined by intraclass correlation coefficients (ICC) and Bland-Altmann plots. Additionally, graders rated the experienced difficulty of each measurement. RESULTS: Intraclass correlation coefficients (ICC) showed excellent inter- and intraobserver reliability with values between 0.994 and 0.998 for RF and slightly higher values for ARPET of 0.997 and 0.999. Bland-Altman plots showed smaller variability for ARPET. Mean interobserver differences (95% CI) for size measurements were -0.11 (-0.27; 0.05) (baseline) and -0.05 mm² (-0.18; 0.08) (follow-up) for RF and -0.04 (-0.14; 0.06) and -0.06 mm² (-0.14; 0.02) for ARPET. Measurements of lesions were on average 0.57 mm² (0.35; 0.79) or 7.6% larger in ARPET. Lesion size between graders did not differ significantly. There was no statistically significant difference in relative enlargement rates between methods. There was poor to moderate agreement between graders when rating the experienced difficulty of each measurement. CONCLUSION: Semi-automated analysis of geographic atrophy with RF and ARPET is equally reliable and reproducible in clinical settings, despite both algorithms require frequent adjustment by users. The ARPET restricts size measurements to the central 5 mm, which limits its ability to fully track GA progression. Results of both tools are not interchangeable as measurements with ARPET result in larger lesion sizes.

Comparison of SD-Optical Coherence Tomography Angiography and Indocyanine Green Angiography in Type 1 and 2 Neovascular Age-related Macular Degeneration.

Purpose: The purpose of this study is to compare the ability of spectral domain optical coherence tomography angiography (SD-OCTA) and indocyanine green angiography (ICGA) to detect and measure lesion area in patients with type 1 and 2 choroidal neovascularization (CNV). Methods: Types 1 and 2 neovascular AMD (nAMD) were included in this prospective and observational case series. ETDRS best-corrected visual acuity (BCVA), ophthalmic examination with funduscopy, OCTA (AngioVue), fluorescein angiography (FA), ICGA, and OCT (Spectralis) were performed. CNV measurements were done manually by two experienced graders using the systems' innate region selection tools. Results: Forty eyes of 39 consecutive patients with nAMD were included. Mean age was 77 ± 6.4 years, ETDRS BCVA was 67 ± 13 letters, and 11 eyes were treatment naïve. Nineteen CNV lesions were classified as type 1 and 21 as type 2. ICGA was able to identify CNV in all eyes. By contrast, OCTA detected CNV in 95% of type 1 and 86% of type 2 nAMD eyes. Mean overall CNV area (CNV-A) was 2.8 ± 2.7 mm2 in ICGA and 2.1 ± 2.7 mm2 in OCTA. Both lesion types CNV-A appeared significantly smaller in OCTA compared with ICGA (P < 0.01). Bland-Altman plot revealed a mean difference (bias) between OCTA and ICGA CNV-A of 0.76 ± 1.74 mm2. Intraclass correlation coefficient (ICC) for CNV-A was 0.91 and 0.93 for ICGA and OCTA, respectively. ICGA CNV-A in the four OCTA-negative eyes (median 4.7 mm2) was not significantly different from the 36 OCTA-positive eyes (median 1.7 mm2). Conclusions: Type 1 and 2 CNV-A were significantly smaller in OCTA than in ICGA. OCTA was generally less successful in detecting CNV than ICGA in patients who were included into this study based on FA and OCT. However, OCTA detected all type 1 lesions except for one, indicating that the SD-OCTA signal is limited by detection limits of blood flow velocity rather than lesion type. Further efforts are needed pushing the limits of lowest detectable and fastest distinguishable flow until OCTA can deliver realistic qualitative and quantitative imaging of type 1 and 2 CNV for diagnosis and monitoring.

ROLE OF ADDITIONAL DEXAMETHASONE FOR THE MANAGEMENT OF PERSISTENT OR RECURRENT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION UNDER RANIBIZUMAB TREATMENT.

PURPOSE: To assess the efficacy of a combination therapy of intravitreal ranibizumab together with a dexamethasone implant in comparison with ranibizumab monotherapy in neovascular age-related macular degeneration. METHODS: Forty eyes of recurrent or persistent neovascular age-related macular degeneration were included in this prospective study. Patients were randomly assigned to two groups. Based on a pro re nata treatment regimen, the first group received intravitreal ranibizumab monotherapy (IVM). The second group received a combination of intravitreal dexamethasone implant and ranibizumab (intravitreal combination [IVC]) at baseline and was retreated with ranibizumab as needed. A second dexamethasone implant was allowed for retreatment after at least 6 months. Retreatment criteria included evidence of subretinal fluid, cystoid macular edema or new hemorrhage, and/or a visual acuity decrease of 5 Early Treatment Diabetic Retinopathy Study letters. RESULTS: During 12 months, a mean of 7.95/5.5 (IVM/IVC; P = 0.042) retreatments were given. The median time until first retreatment differed significantly between the groups (P = 0.004). Functional variables could be maintained in both groups with no differences between them. Visual acuity changed from 62 letters at baseline to 67 at Month 12 in the IVM and remained stable at 68 letters in the IVC group (P = 0.68); macular sensitivity changed from 6.95 dB to 7.01 dB in IVM and from 7.24 dB to 7.12 dB in IVC (P = 0.4). Central retinal thickness decreased, however, with no difference between the groups (P = 0.38). In the IVM/IVC group, 11/12 (55/60%) patients were phakic at the time of study entry. One (9%) patient from the IVM and 4 (33%) from the IVC group were referred to cataract surgery after study completion (P = 0.4). CONCLUSION: This pilot study indicates combined therapy to delay retreatment in patients with persistent/recurrent neovascular age-related macular degeneration and an overall reduction in required ranibizumab retreatments compared with ranibizumab monotherapy with consistent functional outcomes.

Role of adenosine in the control of choroidal blood flow during changes in ocular perfusion pressure.

PURPOSE: The purpose of the present study was to investigate whether the nucleoside adenosine is involved in the regulatory processes of choroidal blood flow (ChBF) during an experimental decrease in ocular perfusion pressure (OPP). METHODS: In this randomized, double-masked, placebo-controlled, two-way crossover study, 14 subjects received either intravenous adenosine or placebo on two different study days. The suction cup method was used for a stepwise increase in intraocular pressure (IOP). Subfoveal ChBF was measured by laser Doppler flowmetry. Mean arterial pressure (MAP) and IOP were measured noninvasively. Ocular perfusion pressure was calculated as OPP = 2/3MAP - IOP. RESULTS: Adenosine increased ChBF significantly versus placebo before application of the suction cup (P < 0.05). When the suction cup was applied, a significant decrease in OPP was observed. This effect was comparable on all study days. The decrease in OPP was paralleled by a significant decrease in ChBF (maximum between -43% and -52%) which was less pronounced than the decrease in OPP (maximum between -62% and -64%). Neither placebo nor adenosine influenced the ChBF increase during suction cup-induced changes in OPP. CONCLUSIONS: The data of the present study confirm that the human choroid shows some regulatory capacity during a decrease in OPP. Adenosine influences basal vascular tone in the choroid but is not involved in the regulatory mechanisms during an increase in IOP. (ClinicalTrials.gov number, NCT00712764.).

Strategies for reducing variance in laser Doppler flowmetry measurements.

BACKGROUND: Scattering of blood flow data as assessed with laser Doppler flowmetry (LDF) in humans is a problem in many studies using this technique. We set out to reduce variability in LDF data by eliminating the effect of the total returning light level (DC) on LDF parameters in the choroid through partial regression analysis. METHODS: In 20 healthy subjects, choroidal blood flow parameters were measured at different DC values using a portable confocal LDF device. We used two different strategies to reduce scattering of data eliminating the effect of yield, which is defined as DC/gain. On the one hand, we used a previously described method based on a third-order polynomial fit, which combines all obtained data. On the other hand, we applied a new method based on a linear fit for each individual subject. RESULTS: Variability of data during changes in DC is higher for LDF parameters volume and flow than for velocity. Both methods were successful in reducing scattering of LDF parameters with varying DC. CONCLUSIONS: The present study indicates that both methods to correct for changes in yield were successful in reducing the variability of LDF measurements. When systematic changes in DC occur after an intervention, one needs to be careful in interpreting the obtained data and it remains to be shown if either of the two techniques is capable of correcting for this effect. The approach presented here may, however, represent an effective, easily applicable and valid approach to reduce scattering of data from using LDF to assess blood flow in the posterior pole of the human eye.