Relationship of choroidal thickness and axial length with posterior vitreous detachment in patients with high myopia.

Although accumulating evidence suggests a higher prevalence of posterior vitreous detachment (PVD) in highly myopic eyes, the relation between ocular biometric features and PVD stages in such eyes remains unclear. Therefore, we enrolled 170 patients with high myopia (axial length ≥ 26.0 mm) to investigate the status of PVD regarding subfoveal choroidal thickness and axial length. Utilising swept-source optical coherence tomography, we classified the PVD status into five stages. The distribution of PVD grades increased as the choroidal thickness decreased and axial length increased (P < 0.01). On adjusting for age and sex, decreased choroidal thickness and increased axial length were associated with more advanced PVD stages: odds ratios with the highest vs. lowest groups were 0.31 (95% confidence interval [CI] 0.09-1.01; Ptrend = 0.009) for choroidal thickness and 5.16 (95% CI 1.34-19.80; Ptrend = 0.002) for axial length. The inverse association between choroidal thickness and PVD status seemed stronger in women than in men (Pinteraction = 0.05). In conclusion, we firstly observed a significant trend of decreased choroidal thickness, along with increased axial length, with increased grade of PVD, particularly among women with highly myopic eyes, suggesting that advanced morphological myopic changes contribute to PVD in middle-aged adults.

Shorter Axial Length Is a Risk Factor for Proliferative Vitreoretinopathy Grade C in Eyes Unmodified by Surgical Invasion.

PURPOSE: To investigate the risk factors for the development of proliferative vitreoretinopathy grade C (PVR-C), independent of prior surgical invasion. METHODS: Patients who underwent surgery for rhegmatogenous retinal detachment were prospectively registered with the Japan-Retinal Detachment Registry, organized by the Japanese Retina and Vitreous Society, between February 2016 and March 2017. Data obtained from general ophthalmic examinations performed before and at 1, 3, and 6 months after surgery were analyzed. RESULTS: We included 2013 eyes of 2013 patients (men, 1326 (65.9%); mean age, 55.2 ± 15.2 years) from amongst 3446 registered patients. Preoperative PVR-C was observed in 3.6% of patients. Propensity score matching revealed that a shorter axial length (AL) was a risk factor for preoperative PVR-C (OR (Odds Ratio), 0.81; 95% CI (Confidence Interval), 0.69 to 0.96; p = 0.015), which was a risk factor for surgical failure (OR, 4.22; 95% CI, 1.12 to 15.93; p = 0.034); the association was particularly significant for eyes with an AL < 25.0 mm (p = 0.016), while it was insignificant for eyes with an AL ≥ 25.0 mm. CONCLUSIONS: A shorter AL was related to the development of PVR-C before surgical invasion. Our results will help elucidate the fundamental pathogenesis of PVR and caution clinicians to meticulously examine eyes with a shorter AL to detect retinal detachment before PVR development.

Assessment of Hypofluorescent Foci on Late-Phase Indocyanine Green Angiography in Central Serous Chorioretinopathy.

To assess the hypofluorescent foci (HFF) on late-phase indocyanine green angiography (ICGA) in central serous chorioretinopathy (CSC) using short-wavelength fundus autofluorescence (SW-FAF), near-infrared autofluorescence (NIR-AF), and fluorescein angiography (FA). The HFF area on late-phase ICGA for at least 20 min was compared with the area of abnormal foci on SW-FAF, NIR-AF, and FA. In 14 consecutive patients (12 men, including 1 with bilateral CSC; and 2 women with unilateral CSC), four kinds of images of 27 eyes were acquired. The mean age ± standard deviation (range) was 46 ± 9.2 years (31-69 years). The HFF on late-phase ICGA were found in 23 eyes (in all 15 CSC eyes and the contralateral 8 eyes). From the results of simple regression analysis, we obtained the following three formulas. The HFF area on ICGA = 1.058 × [abnormal SW-FAF area] + 0.135, the HFF area on ICGA = 1.001 × [abnormal NIR-AF area] + 0.015, and the HFF area on ICGA = 1.089 × [abnormal FA area] + 0.135. Compared to SW-FAF and FA, NIR-AF was found to be the easiest method to detect the HFF on late-phase ICGA, which may indicate melanin abnormalities, especially a decrease, in the retinal pigment epithelium.

Longitudinal Higher-Order OCT Assessment of Quantitative Fluid Dynamics and the Total Retinal Fluid Index in Neovascular AMD.

Purpose: The purpose of this study was to evaluate the feasibility of assessing quantitative longitudinal fluid dynamics and total retinal fluid indices (TRFIs) with higher-order optical coherence tomography (OCT) for neovascular age-related macular degeneration (nAMD). Methods: A post hoc image analysis study was performed using the phase II OSPREY clinical trial comparing brolucizumab and aflibercept in nAMD. Higher-order OCT analysis using a machine learning-enabled fluid feature extraction platform was used to segment intraretinal fluid (IRF) and subretinal fluid (SRF) volumetric components. TRFI, the proportion of fluid volume against total retinal volume, was calculated. Longitudinal fluid metrics were evaluated for the following groups: all subjects (i.e. treatment agnostic), brolucizumab, and aflibercept. Results: Mean IRF and SRF volumes were significantly reduced from baseline at each timepoint for all groups. Fluid feature extraction allowed high-resolution assessment of quantitative fluid burden. A greater proportion of brolucizumab participants achieved true zero and minimal fluid (total fluid volume between 0.0001 and 0.001mm3) versus aflibercept participants at week 40. True zero fluid during q12 brolucizumab dosing was achieved in 36.6% to 38.5%, similar to the 25.6% to 38.5% during the corresponding q8 aflibercept cycles. TRFI was significantly reduced from baseline in all groups. Conclusions: Higher-order OCT analysis demonstrates the feasibility of fluid feature extraction and longitudinal volumetric fluid burden and TRFI characterization in nAMD, supporting a unique opportunity for fluid burden assessment and the impact on outcomes. Translational Relevance: Detection and characterization of disease activity is vital for optimal treatment of nAMD. Longitudinal assessment of fluid dynamics and the TRFI provide important proof of concept for future automated tools in characterizing disease activity.

Fork-shaped mandibular incisors as a novel phenotype of LRP5-associated disorder.

The LRP5 gene encodes a Wnt signaling receptor to which Wnt binds directly. In humans, pathogenic monoallelic variants in LRP5 have been associated with increased bone density and exudative vitreoretinopathy. In mice, LRP5 plays a role in tooth development, including periodontal tissue stability and cementum formation. Here, we report a 14-year-old patient with a de novo non-synonymous variant, p.(Val1245Met), in LRP5 who exhibited mildly reduced bone density and mild exudative vitreoretinopathy together with a previously unreported phenotype consisting of dental abnormalities that included fork-like small incisors with short roots and an anterior open bite, molars with a single root, and severe taurodontism. In that exudative vitreoretinopathy has been reported to be associated with heterozygous loss-of-function variants of LRP5 and that our patient reported here with the p.(Val1245Met) variant had mild exudative vitreoretinopathy, the variant can be considered as an incomplete loss-of-function variant. Alternatively, the p.(Val1245Met) variant can be considered as exerting a dominant-negative effect, as no patients with truncating LRP5 variants and exudative vitreoretinopathy have been reported to exhibit dental anomalies. The documentation of dental anomalies in the presently reported patient strongly supports the notion that LRP5 plays a critical role in odontogenesis in humans, similar to its role in mice.

Retinal Fluid Volatility Associated With Interval Tolerance and Visual Outcomes in Diabetic Macular Edema in the VISTA Phase III Trial.

PURPOSE: To describe longitudinal retinal fluid dynamics on spectral domain OCT and to identify imaging biomarkers that predict the worsening of DME with interval extension during anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: A post hoc sub-analysis of phase III, VISTA-DME study. METHODS: Eyes received either intravitreal aflibercept injection 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly injections (2q8), and eyes imaged with the Cirrus HD-OCT system were included. The macular cube was analyzed for 10 time-points from baseline through week 100. Retinal OCT images were evaluated using a novel software platform to extract retinal fluid features for calculation of volumetric fluid parameters, including the retinal fluid index (RFI): the percentage of retinal volume that was occupied by intraretinal fluid. RESULTS: Fifty-five eyes were included in the 2q4 group, and 58 eyes were included in the 2q8 group. Early RFI volatility with a central macular RFI increase by ≥5 points from week 4 to 8 (P = .004, odds ratio [OR] 31.3, 95% confidence interval [CI] 3.0 to 329) and cumulative RFI volatility with an aggregate increase in macular RFI by ≥10 points from those timepoints with increased RFI between baseline to week 20, P = .005, OR 10.2, 95% CI 2.1 to 51.3) were both significant predictors for the worsening of DME and visual acuity when the treatment interval was extended to 8 weeks in the 2q8 group. CONCLUSIONS: Early fluid dynamics as measured by (1) early RFI volatility and (2) cumulative RFI instability with aggregate increased RFI were associated with intolerance of interval extension.

Risk of newly developing visual field defect and neurodegeneration after pars plana vitrectomy for idiopathic epiretinal membrane.

BACKGROUND/AIMS: Pars plana vitrectomy (PPV) is widely performed in patients with idiopathic epiretinal membrane (iERM) to improve vision. Postoperative visual field defects (VFDs) have been previously reported. However, whether they occur when using the most recent PPV system, and the frequency of VFDs as measured by standard automated perimetry, remain poorly documented and were examined in this study. METHODS: Data of 30 eyes (30 patients; mean age, 66.1 years; 15 men) who underwent PPV for iERM during February 2016-June 2019 and had preoperative and postoperative visual field measurements using standard automated perimetry (Humphrey visual field analyser 30-2 program) were retrospectively analysed. Eyes with diseases other than iERM, including moderate-to-severe cataract or preoperative VFDs were excluded. RESULTS: VFD, defined by the Anderson and Patella's criteria, was found in 73.3% of the eyes 1 month after PPV. After age adjustment, internal limiting membrane (ILM) peeling was identified as a risk factor for postoperative VFD (p=0.035; 95% CI 1.173 to 92.8). Postoperative VFD was frequently observed nasally (86.4%, p=0.002), and on optical coherence tomography measurements, ganglion cell layer (GCL) thinning was found temporal to the fovea (p=0.008). Thinning of the superior and inferior retinal nerve fibre layers and of the GCL temporal to the fovea were significant in eyes after ILM peeling (all p<0.05). CONCLUSION: ILM peeling may cause inner retinal degeneration and lead to the development of VFDs after PPV, which should be further examined.

iOCT-assisted macular hole surgery: outcomes and utility from the DISCOVER study.

BACKGROUND/AIMS: This study aimed to characterise the clinical outcomes and utility of intraoperative optical coherence tomography (iOCT)-assisted macular hole (MH) repair. METHODS: This was a post hoc analysis of eyes in the D etermination of feasibility of I ntraoperative S pectral domain microscope C ombined/integrated O CT V isualization during E n face R etinal and ophthalmic surgery (DISCOVER) study undergoing surgical MH repair with use of iOCT. Functional and surgical outcome data were collected through 12 months postoperatively. MH closure rate, postoperative visual acuity (VA), percentage of cases in which iOCT provided valuable feedback and altered surgical decision making were measured. RESULTS: Eighty-four eyes were included in this study. The mean preoperative VA measured 20/114. The mean postoperative VA improved to 20/68 (p<0.001) at month 1, 20/48 (p<0.001) at month 3 and 20/45 (p<0.001) at month 12 or later. In 43 cases (51%), surgeons reported that iOCT provided valuable information (eg, confirming release of vitreomacular traction and identification of occult residual membranes). In 10 cases (12%), iOCT data specifically altered surgical decision making. Postoperative day 1 transtamponade OCT confirmed tissue apposition and apparent hole closure in 74% of eyes (21/26). All five open holes on postoperative day 1 closed following positioning. Single-surgery MH closure was achieved in 97.6% of cases. One persistent MH was successfully closed with a subsequent surgical repair for a final overall closure rate of 98.8%. Due to chronicity and MH size, additional repair was not recommended for the single remaining persistent MH. CONCLUSION: This study suggests that iOCT may have important utility in MH surgery, including impacting surgical decision making. iOCT-assisted MH surgery resulted in significant improvement in VA and high single-surgery success rate.

Association between axial length and choroidal thickness in early age-related macular degeneration.

The clinical course of age-related macular degeneration (AMD) is related to choroidal conditions, and can be determined by the evaluation of the central choroidal thickness (CCT). The aim of this study was to determine the association between the axial length (AL) and choroidal thickness in AMD by measuring these parameters in patients with and without AMD. Seventy eyes of 70 patients (34 men and 36 women; age, 64-88 years; mean age, 77.0 ± 6.5 years) who underwent cataract surgery from February 2015 to March 2020 at the Department of Ophthalmology, Keio University School of Medicine were retrospectively analyzed. The AMD group (29 patients, 29 eyes) included eyes with early AMD, whereas the control group (41 patients, 41 eyes) included those without ocular diseases other than cataract. Optical coherence tomography images were used to measure the CCT and the choroidal vessel diameter (CVD). The IOL Master was used to measure the AL. The results revealed that mean CCT was greater in the AMD group (238.3 ± 108.3 µm) compared with the age-matched control group (187.2 ± 66.8 µm) (p = 0.03). The CCT was negatively correlated with AL in the overall sample (r = -0.42, p = 0.001), the AMD group (r = -0.42, p = 0.02), and the control group (r = -0.42, p = 0.006). Note that all eyes with CCT > 350 µm were included in the AMD group. CCT and CVD were positively correlated in the overall sample (r = 0.76, p < 0.001) as well as in the individual groups (AMD: r = 0.82, p < 0.001; control: r = 0.76, p = 0.004). Given that CCT is an important parameter for predicting the prognosis of subfoveal diseases, routine evaluation of AL may be valuable for a better understanding of the pathogenesis of AMD.

Correlation between brain volume and retinal photoreceptor outer segment volume in normal aging and neurodegenerative diseases.

PURPOSE: To investigate the association between outer retinal layer metrics, including photoreceptor outer segment volume, on spectral-domain optical coherence tomography (OCT) and brain volume on MRI in normal aging, Alzheimer's disease and Parkinson's disease. METHODS: This was an exploratory analysis of a cross-sectional cohort study that was approved by the Cleveland Clinic Institutional Review Board to evaluate neurodegenerative disorders. Subjects aged ≥ 50 were recruited. A comprehensive neurological exam, brain MRI with volumetric evaluation, and OCT were performed for each subject. Outer retinal layer parameters, including ellipsoid zone (EZ) to retinal pigment epithelium (RPE) volume (i.e., surrogate for panmacular photoreceptor outer segment volume), were evaluated with a novel OCT analysis platform. RESULTS: Of 85 subjects, 64 eyes of 64 subjects met MRI and OCT quality control criteria. Total brain volume (%ICV) significantly correlated with EZ-RPE volume in the normal cognition control group (n = 31, Pearson correlation coefficient 0.514, P < .01), the Parkinson's disease group (n = 19, Pearson correlation coefficient 0.482, P = .04), and the Alzheimer's dementia group (n = 14, Pearson correlation coefficient 0.526, P = .05). Multiple linear regression analysis revealed that photoreceptor outer segment (i.e., EZ-RPE) volume was an independent, influential factor on total brain volume in all study subjects (Coefficient 15.2, 95% confidence interval 7.8-22.6, P < .001). CONCLUSION: Outer retinal parameters on OCT may serve as a novel biomarker related to brain volume. This correlation was noted in control subjects suggesting a possible developmental link between retina and brain volume. This relationship was also maintained with atrophic neurodegenerative disorders. Further research is needed to explore possible threshold differences for underlying neurodegenerative disorders.

Hyperreflective Material in Optical Coherence Tomography Images of Eyes with Myopic Choroidal Neovascularization May Affect the Visual Outcome.

The visual outcome of myopic choroidal neovascularization (CNV) after anti-vascular endothelial growth factor (anti-VEGF) therapy varies among individuals. We retrospectively analyzed the data of 24 eyes (24 patients) with treatment-naïve myopic CNV who underwent anti-VEGF monotherapy following a pro-re-nata regimen at the Division of Medical Retina Clinic, Department of Ophthalmology, Keio University Hospital between May 2014 and December 2017. The mean age was 70.6 ± 2.1 years, and 16 (66.7%) patients were female. Overall, the mean best-corrected visual acuity (BCVA) improved (p = 0.034), and the mean height of the hyperreflective material (HRM), involving the CNV lesion recorded by optical coherence tomography, decreased (p < 0.01) 12 months after the initial treatment. Fifteen eyes (62.5%) achieved a BCVA of better than 0.10 in LogMAR at 12 months; they had a better BCVA (p = 0.015) and lower HRM intensity (p = 0.033) at baseline than the others. Remarkably, the BCVA improved (p < 0.05) and the HRM height (p < 0.01) decreased only in eyes with a final BCVA better than 0.10 as early as 1 month after the initial treatment, which was still present at 12 months. The HRM height and intensity, not only the BCVA, would be valuable in evaluating the prognosis of myopic CNV after anti-VEGF therapy, although further study is required.

Ocular and Systemic Effects of Antioxidative Supplement Use in Young and Healthy Adults: Real-World Cross-Sectional Data.

Randomized controlled studies have shown that antioxidative supplements are effective in suppressing the progression of age-related macular degeneration and visual display terminal syndrome. However, effects of their general use in the real-world and by young and healthy individuals have not been well documented. We analyzed 27 participants who were under 35 years of age and had no diagnosed diseases. Mean functional visual acuity (FVA) score and visual maintenance ratio, which represent quick recognition of a target, both measured using FVA system, were better (both p < 0.01) in subjects who had had regular antioxidative supplement intake for more than 2 months (11 participants) compared with those who had not. Systemic data, i.e., total cholesterol, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) levels, which correspond to chronic low-grade inflammation, were lower (all p < 0.05) in the former. Overall, hs-CRP levels had a correlation with total cholesterol (p < 0.05) and a trend of correlation with HbA1c (p = 0.054) levels. Thus, current real-world data showed that young, healthy participants who had a regular intake of antioxidative supplements had better visual acuity and systemic levels of metabolic and low-grade inflammation markers. This study will help promote future research into the effects of general antioxidative supplement use.

Macular Pigment Optical Density and Photoreceptor Outer Segment Length as Predisease Biomarkers for Age-Related Macular Degeneration.

To explore predisease biomarkers, which may help screen for the risk of age-related macular degeneration (AMD) at very early stages, macular pigment optical density (MPOD) and photoreceptor outer segment (PROS) length were analyzed. Thirty late AMD fellow eyes, which are at high risk and represent the predisease condition of AMD, were evaluated and compared with 30 age-matched control eyes without retinal diseases; there was no early AMD involvement in the AMD fellow eyes. MPOD was measured using MPS2® (M.E. Technica Co. Ltd., Tokyo, Japan), and PROS length was measured based on optical coherence tomography images. MPOD levels and PROS length in the AMD fellow eyes were significantly lower and shorter, respectively, than in control eyes. MPOD and PROS length were positively correlated in control eyes (R = 0.386; p = 0.035) but not in AMD fellow eyes. Twenty (67%) AMD fellow eyes met the criteria of MPOD < 0.65 and/or PROS length < 35 µm, while only five (17%) control eyes did. After adjusting for age and sex, AMD fellow eyes more frequently satisfied the definition (p < 0.001; 95% confidence interval, 3.50-60.4; odds ratio, 14.6). The combination of MPOD and PROS length may be a useful biomarker for screening predisease AMD patients, although further studies are required in this regard.

The Area and Number of Intraretinal Cystoid Spaces Predict the Visual Outcome after Ranibizumab Monotherapy in Diabetic Macular Edema.

Visual outcomes in diabetic macular edema (DME) after anti-vascular endothelial growth factor therapy vary across individuals. We retrospectively reviewed the clinical records for 46 treatment-naive eyes of 46 patients with DME who underwent intravitreal ranibizumab (IVR) monotherapy with a pro re nata regimen for 12 months. Overall, mean best-corrected visual acuity (BCVA) improved. Multivariate analyses adjusted for age and baseline BCVA showed that the area ratio, compared with the retinal area, and the number of intraretinal cystoid spaces evaluated on OCT (optical coherence tomography) images at baseline positively correlated with LogMAR BCVA and the extents of ellipsoid zone and external limiting membrane disruption at 12 months, and negatively correlated with central retinal thickness at the time of edema resolution. Therefore, a high area ratio and large number of intraretinal cystoid spaces resulted in a disorganized outer retinal structure at 12 months, a thin and atrophic retina after edema resolution, and a worse visual outcome. The area ratio and number of intraretinal cystoid spaces on initial OCT images were predictors of the visual outcome after IVR therapy in DME irrespective of baseline age and BCVA. The factors were related to retinal neurodegenerative changes in DME and could help in obtaining proper informed consent before treatment.

Use of OCTA Capillary Perfusion Density Measurements to Detect and Grade Macular Ischemia.

BACKGROUND AND OBJECTIVE: To compare optical coherence tomography angiography (OCTA) capillary perfusion density (CPD) measurements of normal eyes and eyes with macular ischemia (MI). PATIENTS AND METHODS: AVATAR is an institutional review board-approved, prospective, observational imaging study using the Avanti RTVue XR HD. OCTA reports were reviewed for the presence of MI. Qualitative MI grading was performed, and CPD metrics in the superficial and deep fovea and parafovea were analyzed. A normal eye cohort was identified for comparative assessment. RESULTS: The MI and normal cohorts included 55 and 58 eyes, respectively. Compared to normal eyes, eyes with MI had significantly lower CPD values in all regions. There was a statistically significant correlation between qualitative MI grade and VA in the superficial (P = .003) and deep plexuses (P = .029). Only deep parafoveal CPD values demonstrated correlation with VA (P = .043). CONCLUSIONS: Eyes with MI determined by masked qualitative OCTA grading demonstrated significantly reduced CPD values compared to normal eyes. Categorical assessment of MI severity correlated with VA. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S30-S36.].

Correlation between Macular Pigment Optical Density and Neural Thickness and Volume of the Retina.

Macular pigment (MP), which is composed of lutein/zeaxanthin/mezo-zeaxanthin, is concentrated in the central part of the retina, the macula. It protects the macula by absorbing short-wavelength light and suppressing oxidative stress. To evaluate whether MP levels are related to retinal neural protection and resulting health, we analyzed the association between the MP optical density (MPOD), and the macular thickness and volumes. Forty-three eyes of 43 healthy adult volunteers (21 men and 22 women; age: 22-48 (average 31.4 ± 1.1) years) were analyzed. Highly myopic eyes (<-6 diopters) were excluded. MPOD was measured using MPS2®, and the neural retinal thickness and volume were measured using optical coherence tomography. The mean MPOD was 0.589 ± 0.024, and it positively correlated with the central retinal thickness (P = 0.017, R = 0.360) and retinal volume of the fovea (1-mm diameter around the fovea; P = 0.029, R = 0.332), parafovea (1-3-mm diameter; P = 0.002, R = 0.458), and macula (6-mm diameter; P = 0.003, R = 0.447). In the macular area (diameter: 6 mm), MPOD was correlated with the retinal neural volume of the ganglion cell layer (P = 0.037, R = 0.320), inner plexiform layer (P = 0.029, R = 0.333), and outer nuclear layer (P = 0.020, R = 0.353). Thus, MPOD may help in estimating neural health. Further studies should determine the impact of MP levels on neuroprotection.

Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study.

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

Higher-Order Assessment of OCT in Diabetic Macular Edema from the VISTA Study: Ellipsoid Zone Dynamics and the Retinal Fluid Index.

PURPOSE: To investigate retinal fluid features and ellipsoid zone (EZ) integrity dynamics on spectral-domain OCT (SD-OCT) in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept injection (IAI) in the VISTA-DME study. DESIGN: A post hoc subanalysis of a phase III, prospective clinical trial. PARTICIPANTS: Eyes received either IAI 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly doses (2q8). METHODS: All eyes from the VISTA Phase III study in the IAI groups imaged with the Cirrus HD-OCT system (Zeiss, Oberkochen, Germany) were included. The OCT macular cube datasets were evaluated using a novel software platform to generate retinal layer and fluid boundary lines that were manually corrected for assessment of change in EZ parameters and volumetric fluid parameters from baseline. The retinal fluid index (i.e., proportion of the retinal volume consisting of cystic fluid) was also calculated at each time point. MAIN OUTCOME MEASURES: The feasibility of volumetric assessment of higher-order OCT-based retinal parameters and its correlation with best-corrected visual acuity (BCVA). RESULTS: Overall, 106 eyes of 106 patients were included. Specifically, 52 eyes of 52 patients were included in the IAI 2q4 arm, and 54 eyes of 54 patients were included in the IAI 2q8 arm. Ellipsoid zone integrity metrics significantly improved from baseline to week 100, including central macular mean EZ to retinal pigment epithelium (RPE) thickness (2q4: 26.6 µm to 31.6 µm, P < 0.001; 2q8: 25.2 µm to 31.4 µm, P < 0.001). At week 100, central macular intraretinal fluid volume was reduced by >65% (P < 0.001) and central macular subretinal fluid volume was reduced by >99% in both arms (P < 0.001). Central macular retinal fluid index (RFI) significantly improved in both arms (2q4: 17.9% to 7.2%, P < 0.001; 2q8: 19.8% to 4.2%, P < 0.001). Central macular mean EZ-RPE thickness (i.e., a surrogate for photoreceptor outer segment length) and central RFI were independently correlated with BCVA at multiple follow-up visits. CONCLUSIONS: Intravitreal aflibercept injection resulted in significant improvement in EZ integrity and quantitative fluid metrics in both 2q4 and 2q8 arms and correlated with visual function.

Dynamic changes in choroidal conditions during anti-vascular endothelial growth factor therapy in polypoidal choroidal vasculopathy.

We defined the relationships between initial choroidal conditions and their dynamics and exudative changes during anti-vascular endothelial growth factor (anti-VEGF) therapy in polypoidal choroidal vasculopathy (PCV). One hundred treatment-naïve eyes of 100 patients with PCV treated for 24 months at Keio University Hospital with intravitreal ranibizumab or aflibercept monotherapy (three injections and PRN thereafter) were retrospectively analyzed. Wet macula risk after three induction injections, which affected visual prognosis, was predicted by initial pachyvessels in the choroid (foveal greatest vertical choroidal vessel diameter [CVD] ≥180 µm) and pachychoroid (central choroidal thickness [CCT] ≥220 µm) recorded by optical coherence tomography. The risk for recurrent exudative change was greater in the pachyvessel groups irrespective of presence or absence of pachychoroid. Mean CVD and CCT decreased with anti-VEGF therapy when achieving a dry macula, suggesting that exudative changes are regulated by VEGF. Mean CVD and CCT at remission were greater in patients with initial pachyvessels and pachychoroid than in those without; the basal levels of CVD and CCT most likely represent VEGF-unrelated conditions. CVD increase preceded CCT increase and recurrent exudative changes, suggesting that the VEGF-related CVD increase may regulate CCT and exudative change; and that CVD may be a biomarker of exudative change.