An automated process for bulk downloading optical coherence tomography scans.

OBJECTIVE: To develop an automated method for efficiently downloading a large number of optical coherence tomography (OCT) scans obtained using the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) platform. METHODS: The electronic medical records and OCT scans were extracted for all patients with age-related macular degeneration treated at the Hadassah University Hospital Retina Clinic between 2010 and 2021. A macro was created using Visual Basic for Applications (VBA) and Microsoft Excel to automate the export process and anonymize the OCT scans in accordance with hospital policy. OCT scans were extracted as proprietary Heidelberg E2E files. RESULTS: The VBA macro was used to export a total of 94,789 E2E files from 2807 patient records, with an average processing time of 4.32 min per volume scan (SD: 3.57 min). The entire export process took a total of approximately 202 h to complete over a period of 24 days. In a smaller sample, using the macro to download the scans was significantly faster than manually downloading the scans, averaging 3.88 vs. 11.08 min/file, respectively (t = 8.59, p < 0.001). Finally, we found that exporting the files during both off-clinic and working hours resulted in significantly faster processing times compared to exporting the files solely during working hours (t = 5.77, p < 0.001). CONCLUSIONS: This study demonstrates the feasibility of using VBA and Excel to automate the process for bulk downloading data from a specific medical imaging platform. The specific steps and techniques will likely vary depending on the software used and hospital constraints and should be determined for each application.

The pseudohypopyon stage in adult-onset foveomacular vitelliform dystrophy.

PURPOSE: To gain insight into the pathogenesis of adult-onset foveomacular vitelliform dystrophy (AFVD) via assessment of its pseudohypopyon stage (PHS). METHODS: Retrospectively, data were collected in a tertiary center from established cohorts of a genetically evaluated AFVD and best vitelliform macular dystrophy (BVMD) eyes in the pseudohypopyon stage. Best-corrected visual acuity (BCVA, LogMAR), lesion characterization, including lesion dimensions, liquefaction areas and patterns (altitudinal or lateral), and ellipsoid zone integrity were analyzed from spectral-domain optical coherence tomography images. RESULTS: Out of 167 eyes of 90 AFVD patients and 56 eyes of 28 BVMD patients, 8 eyes of six AFVD patients and five eyes of four BVMD patients were at the PHS were included. The mean LogMAR BCVA ± SD was 0.21 ± 0.20 and 0.41 ± 0.10 in AFVD and BVMD diseases, respectively (p = 0.13). Seven AFVD eyes (87.5%) demonstrated lateral liquefaction, while all BVMD eyes demonstrated an altitudinal pattern (p = 0.005). Maximal horizontal lesion diameters were 1.41 ± 0.46 mm and 2.64 ± 0.77 mm in AFVD and BVMD, respectively (p = 0.02). AFVD patients were older (69 ± 14) than BVMD patients (22 ± 13; p = 0.009). CONCLUSION: The pseudohypopyon stage in AFVD is often characterized by a lateral liquefaction pattern, unlike the altitudinal pattern characterizing BVMD. Age, lesion size, or pathogenesis pathways may underline the different pseudohypopyon stage patterns in AFVD and BVMD.

Autoimmune retinopathy: clinical, electrophysiological, and immunological features in nine patients with long-term follow-up.

PURPOSE: We aim to report on the clinical, imaging, immunological, and electrophysiological features of patients with autoimmune retinopathy (AIR) with long-term follow-up. METHODS: Single-center, retrospective study of a consecutive group of AIR patients treated in a tertiary academic medical center. RESULTS: Included were nine patients with a mean ± SD age at presentation of 65 ± 13 years and a median follow-up of 63 months (range 18-120). Five patients were known to have cancer. Median interval between onset of ocular symptoms and diagnosis of AIR was 36 months. Mean baseline and final LogMAR visual acuity were 0.72 ± 0.9 and 1.1 ± 1.2, respectively (p = 0.17). The most common funduscopic findings included optic atrophy and bone-spicule-like pigmentation. Thinning of the nerve fiber layer was the most frequent optical coherence tomographic abnormality. Electroretinographic (ERG) recordings demonstrated variably reduced cone- and rod-derived amplitudes in the majority of eyes at presentation. The most commonly detected anti-retinal antibody was anti-α-enolase. Treatment included immunomodulatory therapy and plasmapheresis. ERG tests showed stability in 64% of eyes throughout the treatment period. CONCLUSION: This study highlights the importance of maintaining a high index of suspicion of AIR, particularly in late middle-aged and elderly patients with "unexplained" visual loss, in light of the non-specific posterior segment signs and the inconsistency of the routinely used ancillary tests.

Endophthalmitis panorama in the Jerusalem area.

PURPOSE: The spectrum of microbial infections and the pattern of their susceptibility are variable among communities. Researching these data will lead to the establishment of the most appropriate national management strategies. The purpose of this study was to analyze the epidemiological, clinical, microbial spectrum and antibiotic susceptibility of endophthalmitis cases in a tertiary referral center in Jerusalem. METHODS: Retrospective review of medical charts of patients presenting with endophthalmitis over a 12-year period. RESULTS: A total of 74 eyes of 70 patients (males 56%) were included. Mean age ± SD at presentation was 60 ± 19.5 years. Exogenous endophthalmitis accounted for 78% of cases, of which 62% followed an intraocular surgery, 21% occurred after intravitreal injections, 10% followed infectious keratitis and 7% were posttraumatic. Endogenous cases were predominantly observed in diabetic patients. Microbial isolates were identified in 44 samples. Of them, gram-positive bacteria were the predominant microorganisms detected in 33 samples (75%); Staphylococcus epidermidis and Enterococcus faecalis were the most commonly detected pathogens. Mean presenting ± SD LogMAR visual acuity (VA) was 2.38 ± 1.21 and it improved at last follow-up to 1.7 ± 1.37 (p = 0.004, paired t test). Cases secondary to gram-positive microbes were associated with improved VA during the follow-up while cases secondary to gram-negative microbes was correlated with poor final VA (p = 0.046, r2 = 0.4). There was no evidence of bacterial resistance in the antibiograms for either vancomycin, ceftazidime, ceftriaxone or amikacin. CONCLUSIONS: Intraocular surgery remains the most common event preceding endophthalmitis with coagulase-negative staphylococci being the most frequently detected microorganisms. The microbial spectrum of endophthalmitis is similar to that in the western world.

Anti-tumor necrosis factor alpha reduces the proangiogenic effects of activated macrophages derived from patients with age-related macular degeneration.

Purpose: Macrophages are believed to promote choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nvAMD); however, the underlying proangiogenic mechanism is poorly understood. Therefore, we examined this mechanism in proinflammatory macrophages derived from patients with nvAMD. Methods: Monocytes were isolated from patients with nvAMD and polarized to form an M1 proangiogenic phenotype. We then screened for the role of proangiogenic cytokines expressed by these macrophages, including TNF-α, VEGF, IL-6, IL-8, and IL-1ß, using an ex vivo choroid sprouting assay and an in vivo rodent model of laser-induced CNV (LI-CNV). We also examined the value of inhibiting TNF-α inhibition with respect to reducing the proangiogenic effects of M1 macrophages. Finally, we analyzed the macrophage cytokine expression database to evaluate the feasibility of modulating the expression of TNF-α. Results: The cytokines above are expressed at high levels in patient-derived M1 macrophages. However, among the cytokines tested only TNF-α significantly increased choroid sprouting. Moreover, adoptive intravitreal transfer of M1 macrophages significantly increased LI-CNV, and blocking TNF-α abolished the proangiogenic effects of M1 macrophages in both models. An analysis of cytokine expression revealed that >50% of TNF-α expression is determined by modifiable factors. Conclusions: Blocking TNF-α can reduce the proangiogenic effects of M1 macrophages in nvAMD. Thus, activated macrophages may represent a potential therapeutic target for altering TNF-α expression in nvAMD.

Topography of choriocapillaris flow deficit predicts development of neovascularization or atrophy in age-related macular degeneration.

PURPOSE: To evaluate the relationship between choriocapillaris (CC), flow deficits (FD), and structural optical coherence tomography (OCT) biomarkers, and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy (cRORA) or macular neovascularization (MNV). METHODS: Consecutive patients with iAMD were sequentially reviewed to define three equal sized groups: progressed to MNV, progressed to cRORA, or remained stable over 12 months of follow-up. Odds ratios for progression to cRORA and MNV were estimated by logistic regression for intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDDs), high central drusen volume, fellow eye with late AMD, and peripheral and central CC FD. RESULTS: Thirty iAMD eyes from 30 patients were enrolled into each group. The CC FD was greater in the peripheral sectors of the macula of eyes which progressed to cRORA compared to the other two groups (P < 0.0001). The central CC FD was also significantly impaired in eyes that progressed to cRORA or MNV compared to eyes that did not progress (P = 0.001 and P = 0.02, respectively). CC FD in the peripheral macula was significantly and independently associated with the development of cRORA, while CC FD in the center was significantly and independently associated with the development of MNV. CONCLUSIONS: While the CC is diffusely impaired throughout the macula in iAMD eyes that progress to cRORA, it is relatively spared in the more peripheral macula among eyes which progress to MNV. These differential findings may have implications for the pathophysiology of the different late-stage manifestations of AMD.

TOPOGRAPHIC ASSESSMENT OF CHORIOCAPILLARIS FLOW DEFICITS IN THE INTERMEDIATE AGE-RELATED MACULAR DEGENERATION EYES WITH HYPOREFLECTIVE CORES INSIDE DRUSEN.

PURPOSE: To evaluate the choriocapillaris (CC) flow deficit (FD) in eyes with hyporeflective cores (HCs) inside drusen in eyes with intermediate age-related macular degeneration. METHODS: Intermediate age-related macular degeneration subjects underwent optical coherence tomography and optical coherence tomography angiography using a Cirrus HD-optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). All B-scans were inspected for the presence of drusen with an HC that was defined as dark, condense materials inside drusen. Drusen regions delineated in the manufactures advanced retinal pigment epithelium elevation map were superimposed to the compensated CC optical coherence tomography angiography images. Quantitative analysis of CC FD% was performed under drusen with and without HCs, 150-µm-wide ring region around drusen with and without HCs, drusen-free region, and whole macula. RESULTS: Fifty eyes were included in this cross-sectional study. Twenty eyes had drusen with HCs. Thirty eyes without HCs were matched for age and sex. The CC FD% of whole macula was significantly greater in eyes with an HC than those without it (46.3% vs. 42.9%; P = 0.001). In eyes with HCs, regional CC FD% was the greater under drusen (59.8%) and in a 150-µm-wide ring surrounding drusen with HCs (53.0%) than corresponding regions for drusen without HCs (52.5% and 47.3%, respectively) (P < 0.005 in all, Bonferroni correction). The CC FD% in macular regions remote from drusen was 43.2%. CONCLUSION: Intermediate age-related macular degeneration eyes with HCs demonstrated more impaired CC flow, compared with those without this featured. The CC was also more severely impaired directly below these drusen with HCs. These findings highlight that the appearance of HCs may be an indicator of a more advanced disease phenotype.

CHORIOCAPILLARIS FLOW DEFICITS AS A RISK FACTOR FOR PROGRESSION OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the association between choriocapillaris (CC) flow deficits and structural optical coherence tomography biomarkers and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy. METHODS: Retrospective analysis of consecutive patients with iAMD with a minimum follow-up of 12 months. Odds ratios of intraretinal hyperreflective foci, hyporeflective drusen cores, subretinal drusenoid deposits, the presence of drusen volume ≥0.03 mm3 within a central 3-mm circle, fellow eye with late stage of AMD, and CC flow deficits at baseline and months of follow-up were estimated from logistic regression. RESULTS: A total of 112 eyes with iAMD were included. Eyes that progressed were significantly more likely to show intraretinal hyperreflective foci, hyporeflective drusen cores, and drusen volume ≥0.03 mm3. The CC flow deficit was also significantly greater in eyes that developed complete retinal pigment epithelial and outer retinal atrophy. Intraretinal hyperreflective foci, hyporeflective drusen cores, drusen volume ≥0.03 mm3, and higher CC flow deficits were significantly and independently associated with the development of complete retinal pigment epithelial and outer retinal atrophy. CONCLUSION: The CC flow deficit was significantly greater in iAMD eyes that progressed to complete retinal pigment epithelial and outer retinal atrophy and remained an independent risk factor when structural optical coherence tomography biomarkers were considered. CC flow deficits may be useful for enhancing risk stratification and prognostication of patients with iAMD.

Choriocapillaris flow deficit associated with intraretinal hyperreflective foci in intermediate age-related macular degeneration.

PURPOSE: To evaluate the choriocapillaris (CC) flow deficit (FD) beneath drusen associated with overlying intraretinal hyperreflective foci (HRF). METHODS: Patients with intermediate age-related macular degeneration (AMD) who had structural spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) using the Cirrus HD-OCT with AngioPlex software were retrospectively evaluated. A 6 × 6-mm-volume scan was used for the SD-OCT and OCTA. Post-imaging processing steps included generation of drusen map, identification of HRF, and generation of a signal-compensated CC slab prior to binarization and CC FD computation. The CC OCTA image was aligned with the drusen + HRF map to define regions of interest for CC FD measurement. The CC was quantified below drusen with and without overlying HRF and within a 150-µm-wide ring surrounding the drusen (unaffected by potential HRF-related shadowing), and across the entire 6 × 6 macular region. RESULTS: Fifty-three eyes with intermediate AMD were included, 25 eyes with HRF, and 28 eyes with no HRF. The mean ± SD FD% over the whole 6 × 6 macular region was 41.1 ± 3.4 in eyes with HRF compared with 39.5 ± 3.5 in eyes without HRF (p = 0.001). The mean ± SD CC FD% below drusen with HRF (54.4 ± 9.3) was significantly greater than below drusen without HRF (49.6 ± 9.5; p = 0.001). There was a strong positive correlation between the quantity of HRF and the extent of the CC FD (Pearson correlation = 0.81). CONCLUSION: Choriocapillaris flow deficits appear to be more severe in eyes with HRF and in particular directly below HRF. As HRF are thought to represent a higher risk or more advanced feature of intermediate AMD, these findings highlight the relationship between the severity of CC FD and overall severity of AMD.

QUANTITATIVE ASSESSMENT OF CHORIOCAPILLARIS FLOW DEFICITS SURROUNDING CHOROIDAL NEOVASCULAR MEMBRANES.

PURPOSE: To quantify the regional variation in choriocapillaris (CC) flow deficits percentage (FD%) surrounding treatment-naïve Type 1 choroidal neovascularization (CNV) associated with age-related macular degeneration. METHODS: Patients were imaged with swept-source optical coherence tomography angiography system (Carl Zeiss PLEX Elite 9000; Carl Zeiss Meditec AG, Jena, Germany). Two 6 × 6-mm volume scans were acquired. Boundary-specific segmentation was used to isolate the Type 1 CNV. For CC assessment, both structural and optical coherence tomography angiography CC slabs (10-µm thick, starting 21 µm below the retinal pigment epithelium fit reference) were exported for signal compensation and averaging using ImageJ. The resultant CC image was binarized to calculate the FD%, for para-CNV and peri-CNV rings (each 500-µm wide). In a subgroup of 20 eyes, the FD% was compared with similar regions of age-matched controls. The FD% was also analyzed in small 500 × 500-µm squares equidistant from the fovea to compensate for regional variation of CC FD% as a potential confounding factor. RESULTS: Thirty-two eyes from 27 subjects were enrolled in this study. The CC FD% in the para-CNV ring was 26.58 ± 7.36, which was significantly higher than the peri-CNV ring (21.94 ± 6.31); P < 0.001. The FD% in para-CNV and peri-CNV rings was significantly greater than that of healthy controls (15.82 ± 1.29% and 15.53 ± 1.32%, respectively); P < 0.001. The FD% computed in the 500-µm squares equidistant from the fovea was also greater in the para-CNV ring (26.14 ± 7.11) than that in the peri-CNV ring (22.31 ± 6.21); P < 0.001. CONCLUSION: Choriocapillaris FD% is the highest in the region immediately surrounding the CNV.

Anomaly Detection and Biomarkers Localization in Retinal Images.

Background: To design a novel anomaly detection and localization approach using artificial intelligence methods using optical coherence tomography (OCT) scans for retinal diseases. Methods: High-resolution OCT scans from the publicly available Kaggle dataset and a local dataset were used by four state-of-the-art self-supervised frameworks. The backbone model of all the frameworks was a pre-trained convolutional neural network (CNN), which enabled the extraction of meaningful features from OCT images. Anomalous images included choroidal neovascularization (CNV), diabetic macular edema (DME), and the presence of drusen. Anomaly detectors were evaluated by commonly accepted performance metrics, including area under the receiver operating characteristic curve, F1 score, and accuracy. Results: A total of 25,315 high-resolution retinal OCT slabs were used for training. Test and validation sets consisted of 968 and 4000 slabs, respectively. The best performing across all anomaly detectors had an area under the receiver operating characteristic of 0.99. All frameworks were shown to achieve high performance and generalize well for the different retinal diseases. Heat maps were generated to visualize the quality of the frameworks' ability to localize anomalous areas of the image. Conclusions: This study shows that with the use of pre-trained feature extractors, the frameworks tested can generalize to the domain of retinal OCT scans and achieve high image-level ROC-AUC scores. The localization results of these frameworks are promising and successfully capture areas that indicate the presence of retinal pathology. Moreover, such frameworks have the potential to uncover new biomarkers that are difficult for the human eye to detect. Frameworks for anomaly detection and localization can potentially be integrated into clinical decision support and automatic screening systems that will aid ophthalmologists in patient diagnosis, follow-up, and treatment design. This work establishes a solid basis for further development of automated anomaly detection frameworks for clinical use.

Impact of slab selection on the relationship between choriocapillaris flow deficits and enlargement rate of geographic atrophy.

OBJECTIVE: To evaluate the effect of changing slab position on the correlation between choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) and yearly enlargement rate (yER) of GA. METHODS: OCT and OCTA images obtained on Cirrus HD-OCT device were collected from patients with GA. Each patient underwent OCTA scan at baseline and two OCT scans, one at baseline and one after at least 12 months. GA was delineated on en-face fundus image to calculate yER. OCTA images were generated from three 10 µm thick slabs 11, 21 and 31 µm posterior to RPE-fit line. 100 µm-wide concentric rings were generated around GA to calculate FD% in each ring which was correlated with yER. RESULTS: For the 11-21 µm slab, FD% was not significantly correlated with yER for any of the rings (p > 0.05). For the 21-31 and 31-41 µm slab, FD% of rings located in the 600 µm region around GA was significantly correlated with yER (p < 0.05). However, in all slab locations, there was no significant correlation between yER and CC FD% of rings located beyond the 600 µm region (p > 0.05). CONCLUSIONS: Slab selection for quantification of CC FD% may have a significant impact on quantitative results in eyes with GA.

Genome wide association study and genomic risk prediction of age related macular degeneration in Israel.

The risk of developing age-related macular degeneration (AMD) is influenced by genetic background. In 2016, the International AMD Genomics Consortium (IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score (PRS) from these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish (AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study (GWAS) for AMD in Israel, and to evaluate PRSs for AMD. Our discovery set recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary-statistics excluding our study and developed PRSs via clumping/thresholding or LDpred2. In our discovery set, 31/34 loci reported by IAMDGC were AMD-associated (P < 0.05). Of those, all effects were directionally consistent with IAMDGC and 11 loci had a P-value under Bonferroni-corrected threshold (0.05/34 = 0.0015). At a 5 × 10-5 threshold, we discovered four suggestive associations in FAM189A1, IGDCC4, C7orf50, and CNTNAP4. Only the FAM189A1 variant was AMD-associated in the replication cohort after Bonferroni-correction. A prediction model including LDpred2-based PRS + covariates had an AUC of 0.82 (95% CI 0.79-0.85) and performed better than covariates-only model (P = 5.1 × 10-9). Therefore, previously reported AMD-associated loci were nominally associated with AMD in Israel. A PRS developed based on a large international study is predictive in Israeli populations.

Genome-wide association study and genomic risk prediction of age-related macular degeneration in Israel.

Purpose: The risk of developing age-related macular degeneration(AMD) is influenced by genetic background. In 2016, International AMD Genomics Consortium(IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score(PRS) based on these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish(AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study(GWAS) for AMD in Israel, and to evaluate PRSs for AMD. Methods: For our discovery set, we recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped all individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary statistics excluding our study and developed PRSs via either clumping/thresholding or LDpred2. Results: In our discovery set, 31/34 loci previously reported by the IAMDGC were AMD associated with P<0.05. Of those, all effects were directionally consistent with the IAMDGC and 11 loci had a p-value under Bonferroni-corrected threshold(0.05/34=0.0015). At a threshold of 5x10 -5 , we discovered four suggestive associations in FAM189A1 , IGDCC4 , C7orf50 , and CNTNAP4 . However, only the FAM189A1 variant was AMD associated in the replication cohort after Bonferroni-correction. A prediction model including LDpred2-based PRS and other covariates had an AUC of 0.82(95%CI:0.79-0.85) and performed better than a covariates-only model(P=5.1x10 -9 ). Conclusions: Previously reported AMD-associated loci were nominally associated with AMD in Israel. A PRS developed based on a large international study is predictive in Israeli populations.

SLIViT: a general AI framework for clinical-feature diagnosis from limited 3D biomedical-imaging data.

We present SLIViT, a deep-learning framework that accurately measures disease-related risk factors in volumetric biomedical imaging, such as magnetic resonance imaging (MRI) scans, optical coherence tomography (OCT) scans, and ultrasound videos. To evaluate SLIViT, we applied it to five different datasets of these three different data modalities tackling seven learning tasks (including both classification and regression) and found that it consistently and significantly outperforms domain-specific state-of-the-art models, typically improving performance (ROC AUC or correlation) by 0.1-0.4. Notably, compared to existing approaches, SLIViT can be applied even when only a small number of annotated training samples is available, which is often a constraint in medical applications. When trained on less than 700 annotated volumes, SLIViT obtained accuracy comparable to trained clinical specialists while reducing annotation time by a factor of 5,000 demonstrating its utility to automate and expedite ongoing research and other practical clinical scenarios.

Correlation of response to intravitreal bevacizumab treatment between the first and second treated eyes in diabetic macular edema.

PURPOSE: To evaluate whether outcome of bevacizumab treatment in the first treated eye can guide the selection of compound for the second treated eye in patients with bilateral diabetic macular edema. METHODS: Demographic, clinical, and optical coherence tomography data were retrospectively collected from consecutive patients who underwent bevacizumab therapy for bilateral diabetic macular edema. Change in central subfield thickness and visual acuity were evaluated and compared between the first treated eye and second treated eye. RESULTS: A total of 66 eyes of 33 patients were included in the study. The mean ± SD follow-up time was 13 ± 5 months. The mean ± SD central subfield thickness at baseline was 464 ± 30 µm in the first treated eye and 461 ± 29 µm in the second treated eye (p = 0.91). Final central subfield thickness was reduced to 392 ± 27 µm in the first treated eye (p = 0.01 compared with baseline) and 416 ± 25 µm in the second treated eye (p = 0.03 compared with baseline). Using ≥5% or ≥10% reduction of central subfield thickness as diagnostic criteria to predict similar magnitude of thickness reduction in the first treated eye yielded a positive and negative predictive value ranging from 46% to 81%, and sensitivity and specificity ranging from 54% to 84%. Regression models did not show correlation between central subfield thickness reduction in first treated eye and the second treated eye at the end of follow-up. CONCLUSIONS: Bevacizumab therapy reduced macular thickness in both eyes in bilateral diabetic macular edema. Treatment outcome of the first treated eye could not predict the outcome of the second treated eye. Particularly, failure to reduce central subfield thickness in the first treated eye does not preclude a favorable response to bevacizumab therapy in the second eye.

Progression of choriocapillaris flow deficits in clinically stable intermediate age-related macular degeneration.

PURPOSE: To evaluate the choriocapillaris (CC) flow deficit (FD) in eyes with stable intermediate age-related macular degeneration (AMD) eyes over 12 months of follow-up. METHODS: Thirty four patients with intermediate AMD were prospectively enrolled and evaluated by swept-source optical coherence tomography (SS-OCT) and OCT-angiography (OCTA) using the PLEX-Elite 9000. A 6 × 6 mm foveal-centered scan was used for both modalities and the study eyes were scanned twice to allow subsequent averaging. En face OCTA CC slabs (31-41 µm below the RPE-band) were exported and compensated for signal attenuation. Two compensated CC en-face images were registered and averaged prior to binarization and CC FD computation. The CC FD of the entire 6 × 6 macular region was quantified at baseline and at 12-months. The presence of high-risk features, namely intraretinal hyper-reflective foci (HRF), subretinal drusenoid deposits (SDD), and hyporeflective-core-drusen, were evaluated using SS-OCT volume scans. RESULTS: Among the 34 eyes, 25 eyes from 25 patients were noted on exam and OCT to remain stable as intermediate AMD at 12-months without the development of late AMD. Eleven eyes had high-risk features at baseline compared to 14 eyes at the end of the follow-up (p = 0.094). The mean ± SD FD% across the whole 6 × 6 macular region at baseline was 19.32 ± 4.64% and significantly increased to 28.62 ± 4.71% at the end of the study (p = 0.001). The CC FD progressed significantly both in non-HR and HR-eyes. CONCLUSIONS: Choriocapillaris flow impairment significantly deteriorated over one year in relatively stable intermediate AMD. This might suggest that underlying progression of CC dysfunction occurs before structural changes appears on OCT and lead to the progression to late-stage AMD.

Correlation of Response between Both Eyes to First- and Second-Line Anti-VEGF Therapy in Diabetic Macular Edema.

PURPOSE: To evaluate the anatomical correlation between fellow eyes for bilateral second-line anti-VEGF treatment in eyes with bilateral diabetic macular edema (DME) with incomplete response to first-line bevacizumab therapy. METHODS: Seventy-four eyes (n = 37 patients) with bilateral-DME having incomplete response to first-line bevacizumab therapy that were switched for bilateral treatment with ranibizumab were retrospectively evaluated. Data collected included demographics, visual acuity and macular thickness. We evaluate the correlation for the response of both eyes in terms of macular thickness and visual acuity. RESULTS: The mean±SD age was 76 ± 8 years. The mean±SD number of bevacizumab injections prior the switch was 11.03 ± 5.1 in the first eye (FE) and 10.9 ± 5.2 in the second eye (SE). The central subfield thickness (CST) reduced from 472 ± 171 microns at baseline to 418 ± 161 after the last bevacizumab injection and 365 ± 74 after 3 ranibizumab injections in the FE (p = .016, p = .004, respectively), and from 463 ± 145 microns to 446 ± 123, and 421 ± 103 in the SE (p = .112, p = .001, respectively). There was strong positive correlation between the eyes for the CST reduction under bevacizumab and ranibizumab treatments in each visit. BCVA± SD at baseline was 0.41 ± 0.30 LogMAR in the FE, and 0.42 ± 0.29 in the SE (p = .44). After 3 injections of bevacizumab, the BCVA was 0.37 ± 0.26 and 0.42 ± 0.23 in FE and SE respectively (p = .013, p = .132, respectively). CONCLUSIONS: This study demonstrated a strong anatomical correlation responses between the eyes in patients with bilateral DME for both first-line bevacizumab therapy and second-line ranibizumab therapy. Response to second-line therapy was favorable and correlated among eyes regardless they were from the same or different individuals.

Analysis of the Aqueous Humor Proteome in Patients With Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is associated with altered gene and protein expression in the retina. We characterize the aqueous humor (AH) proteome in AMD to gain insight into the pathogenesis of the disease and identify potential biomarkers. Methods: AH was collected from age and gender matched neovascular AMD (nvAMD; n = 10) patients and controls (n = 10). AH was pooled to create two samples (nvAMD and control), followed by intensity-based label-free quantification (MS1). Functional and bioinformatic analysis were then performed. A validation set (20 controls, 15 atrophic AMD and 15 nvAMD) was tested via multiplex ELISA for nine differentially expressed proteins according to the MS1 findings. Results: MS1 identified 674 proteins in the AH. 239 proteins were upregulated in nvAMD (nvAMD/control > 2, peptide tags (PT) > 2), and 86 proteins were downregulated (nvAMD/control < 0.5, PT > 2). Functional analysis of proteins upregulated in AMD demonstrated enrichment for platelet degranulation (enrichment score (ES):28.1), negative regulation of endopeptidase activity (ES:18.8), cellular protein metabolic process (ES:11.8), epidermal growth factor-like domain (ES:10.3), sushi/SCR/CCP (ES:10.1), and complement/coagulation cascades (ES:9.2). AMD protein clusters were upregulated for 3/6 (χ2 < 0.05 compared to randomization). Validation via ELISA confirmed MS1 in 2/9 proteins (Clusterin and Serpin A4, P < 0.05), while 3/9 showed differential expression between aAMD and nvAMD (Clusterin, Serpin A4, and TF P < 0.05). Receiver operating characteristic curve calculation identified the area under the curve of 0.82 for clusterin as a biomarker for distinction of AMD. Conclusions: AH proteomics in AMD patients identified several proteins and functional clusters with altered expression. Further research should confirm if these proteins may serve as biomarkers or therapeutic target for the disease.

Scotopic microperimetric sensitivity and inner choroid flow deficits as predictors of progression to nascent geographic atrophy.

BACKGROUND/AIMS: To assess the role of microperimetric retinal sensitivity (MPRS) and inner choroid flow deficits (IC FD) in predicting the development of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) in intermediate AMD (i-AMD). METHODS: Thirty eyes with i-AMD evaluated at the Doheny-UCLA Eye Centres were enrolled in this prospective IRB-approved study. Subjects underwent several diagnostic tests: (a) 6×6 mm swept-source optical coherence tomography angiography (SS-OCTA) with the IC slab used to quantify the FDs, (b) 20°×20° spectral-domain optical coherence tomography (SD-OCT) to monitor progression to iRORA and (c) scotopic MPRS within an area of 18° centred on the fovea. All subjects were followed-up for 24 months. The baseline IC FD and MPRS were correlated with the development of iRORA. At 24-month follow-up, the stage of AMD was re-assessed and the eyes were divided into two sub-groups based on the development of iRORA. RESULTS: Twenty-eight eyes completed the 2-year follow-up. At baseline, the mean MPRS was 13.40±4.66 dB and the mean IC FD was 27.55±8.67%. The morpho-functional regression showed a significant correlation between baseline MPRS and IC FD and the development of iRORA within 24 months (R2=0.744, p<0.05). A Kaplan-Meier survival curve was fit to determine the cumulative incidence of iRORA over the 24 months. CONCLUSIONS: A lower MPRS and greater IC FD at baseline were predictors of progression to iRORA in eyes with i-AMD. These parameters may be useful biomarkers for risk stratification and prognostication.