Retinal arterial and vein occlusion: is surgery ever indicated?

PURPOSE OF REVIEW: To highlight the recent progression in surgical treatments for central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO). RECENT FINDINGS: Anti-VEGF treatment, accepted as a primary treatment for CRVO, is unable to effectively treat all types of the diseases. Regarding CRAO, there are not any accepted therapies available. There have however been recent innovations in surgery, such as utilizing robotics-assisted tools in cannulation procedures for central retinal artery occlusion, or micro-cystotomy for refractory macular edema resulting from ischemic CRVO. SUMMARY: Refractory macular edema due to CRVO can be treated with aspiration of the fluid found inside the large cysts often seen in edema. The success rate of micro-cystotomy has been reported at 78% in eyes with refractory macular edema. Recent studies have shown that cannulation with tissue plasminogen activator (tPA) is effective for eyes with CRAO due to thrombus.Recent cannulation or micro-cystotomy procedures can be enhanced with the use of robotic tools which allow us to perform this difficult procedure more easily. Newly developed technology, and consequent developments in surgical procedures, will allow us to deal with unmet needs for retinal vessel occlusive diseases.

Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration.

PURPOSE: This study aimed to compare functional and morphologic changes in the loading phase between patients with treatment-naïve macular neovascularization (MNV) due to neovascular age-related macular degeneration (nAMD) treated with either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. METHODS: We retrospectively studied 92 consecutive eyes of 90 patients with neovascular nAMD who were scheduled to receive IVBr (42 eyes of 41 patients) or IVF (50 eyes of 49 patients) injections between October 2021 and December 2022. All patients received three consecutive monthly injections of 6.0 mg/0.05 mL brolucizumab or 6.0 mg/0.05 mL faricimab. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and central choroidal thickness (CCT) at baseline and 1, 2, and 4 months after the initial treatment were measured and compared between the groups. RESULTS: Thirty-seven eyes in IVBr group and forty-seven eyes in IVF group who finished treatments in the loading phase were assessed at the follow-up examination. The BCVA, CFT, and CCT changed significantly after loading phase in both groups (P < 0.05 for both comparisons). The IVBr group had more rapid improvement of the BCVA (P = 0.037) at 1 month than the IVF group, but there was no difference at 4 months (P = 0.367). The CFT and CCT decreases tended to be greater in the IVBr group than in the IVF group throughout the follow-up period. Of the five eyes excluded from the IVBr group, one eye (2.4%) each had intraocular inflammation (IOI) and was a non-responder, and two eyes (4.8%) had retinal pigment epithelial tears after treatment. Of the three eyes excluded from the IVF group, two eyes (4.0%) did not respond to the treatment. CONCLUSIONS: Both IVBr and IVF injections were well-tolerated and improved the VA in treatment-naïve patients with MNV due to nAMD after a loading phase, although IVBr caused a trend toward faster visual improvements in the BCVA. The IVBr group also had greater reductions of the CFT and CCT than the IVF group. However, the potential for adverse events and no response to treatment with each drug are considerations.

INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

An AI model to estimate visual acuity based solely on cross-sectional OCT imaging of various diseases.

PURPOSE: To develop an artificial intelligence (AI) model for estimating best-corrected visual acuity (BCVA) using horizontal and vertical optical coherence tomography (OCT) scans of various retinal diseases and examine factors associated with its accuracy. METHODS: OCT images and associated BCVA measurements from 2,700 OCT images (accrued from 2004 to 2018 with an Atlantis, Triton; Topcon, Tokyo, Japan) of 756 eyes of 469 patients and their BCVA were retrospectively analysed. For each eye, one horizontal and one vertical OCT scan in cross-line mode were used. The GoogLeNet architecture was implemented. The coefficient of determination (R2), root mean square error (RMSE) and mean absolute error (MAE) were computed to evaluate the performance of the trained network. RESULTS: R2, RMSE, and MAE were 0.512, 0.350, and 0.321, respectively. R2 was higher in phakic eyes than in pseudophakic eyes. Multivariable regression analysis showed that a higher R2 was significantly associated with better BCVA (p < 0.001) and a higher standard deviation of BCVA (p < 0.001). However, the performance was worse in an external validation, with R2 of 0.19. R2 values for retinal vein occlusion and age-related macular degeneration were 0.961 and 0.373 in the internal validation but 0.20 and 0.22 in the external validation. CONCLUSION: Although underspecification appears to be a fundamental problem to be addressed in AI models for predicting visual acuity, the present results suggest that AI models might have potential for estimating BCVA from OCT in AMD and RVO. Further research is needed to improve the utility of BCVA estimation for these diseases.

Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.

PURPOSE: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD). METHODS: Treatment-naïve patients with nAMD were randomly assigned (1:1) to faricimab 6.0 mg up to every 16 weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0 mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. RESULTS: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n = 61; aflibercept n = 59) and non-Asian country (faricimab n = 604; aflibercept n = 605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved ≥ Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile. CONCLUSION: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03823287 (TENAYA); NCT03823300 (LUCERNE). Date of registration: January 30, 2019.

ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY IN DETERMINATION OF ENTRY SITE FOR VITRECTOMY IN HIGHLY MYOPIC EYES.

PURPOSE: To evaluate the efficacy of anterior segment optical coherent tomography (AS OCT) in estimating the length of the pars plana and optimizing the sclerotomy entry site in vitrectomy for highly myopic eyes, facilitating membrane peeling. METHODS: Twenty-three eyes with myopic traction maculopathy were studied. The pars plana was examined using two methods: preoperative AS OCT and intraoperative measurement. The distance from the limbus to the ora serrata in two groups was measured to compare differences in length. The actual length of the entry site from the limbus and forceps used were noted in all eyes studied. RESULTS: The mean axial length was 29.2 ± 2.3 mm for all 23 eyes. The average length between the limbus and ora serrata measured with AS OCT and intraoperative examination was 6,710 µ m (SD ± 459) and 6,671 µ m (SD ± 402), respectively, in the superotemporal region ( P > 0.05), and 6,340 µ m (SD ± 321) and 6,204 µ m (SD ± 402), respectively, in the superonasal region ( P >0.05). The mean length of the entry site from the limbus was 6.2 mm, and 28-mm forceps were used in 17 of 23 eyes (77%). CONCLUSION: The length of the pars plana varies depending on the axial length of the eye. Preoperative AS OCT enables accurate measurement of the pars plana in eyes with high myopia. AS OCT examination can help determine the optimal site for sclerotomy, allowing easier access to the macular region for membrane peeling in highly myopic eyes.

IMPACT OF GAS/AIR TAMPONADE ON REFRACTIVE OUTCOMES AFTER FLANGED INTRASCLERAL INTRAOCULAR LENS FIXATION.

PURPOSE: This study aims to investigate the postoperative refractive outcomes in eyes that underwent the flanged intrascleral intraocular lens (IOL) fixation combined with vitrectomy with or without gas/air tamponade. METHODS: The eyes were divided into two groups (Group A; eyes that underwent flanged intrascleral IOL fixation with gas/air tamponade, and Group B; eyes that underwent flanged intrascleral IOL fixation without gas/air tamponade). The predicted spherical equivalent (SE) refraction values were calculated using the Sander-Retzlaff-Kraff Theoretical formula. Then, the prediction error was calculated by subtracting the predicted SE refraction from the postoperative objective SE refraction and the absolute prediction error was calculated as the absolute value of the prediction error for each eye. RESULTS: A total of 68 eyes were included in the current study. There was a significant correlation between the predicted and postoperative SE refraction in both groups (Group A, r = 0.968, P < 0.0001, Group B, r = 0.943, P < 0.0001, linear regression analysis). The prediction error demonstrated a mild myopic shift after the flanged intrascleral IOL fixation in both groups (Group A, -0.40 ± 0.96 diopter, Group B, -0.59 ± 0.95 diopter). There was no significant difference in prediction error and absolute prediction error between the two groups ( P = 0.44, P = 0.70, Wilcoxon rank sum test). CONCLUSION: The postoperative SE refraction after flanged intrascleral IOL fixation was not influenced by gas/air tamponade.

PATTERN AND CHARACTERISTICS OF DRUSEN SUBTYPES IN CHINESE AND INDIAN POPULATIONS IN SINGAPORE.

PURPOSE: To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness. METHODS: This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness. RESULTS: Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 µm; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 µm; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 µm; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 µm; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed. CONCLUSION: Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.

Hyperreflective material in patients with non-neovascular pachychoroid disease.

BACKGROUND: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients. METHODS: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes. RESULTS: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period. CONCLUSION: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Cytokine profiles of macular neovascularization in the elderly based on a classification from a pachychoroid/drusen perspective.

PURPOSE: To classify macular neovascularization (MNV) based on pachychoroid and drusen features and to examine the aqueous humor cytokine signatures of each group. METHODS: In total, 106 consecutive eyes with treatment-naïve MNV and 104 control eyes were examined. The aqueous humor concentrations of 15 cytokines were compared among the MNV groups classified based on the presence of drusen and/or pachychoroid features. Multidimensional scaling analysis was used to visualize the similarity level of the MNV subtypes according to their cytokine profiles. RESULTS: Thirty-one, 18, 43, and 10 eyes were classified into the pachychoroid-associated, drusen-associated, pachychoroid/drusen-associated, and non-drusen/non-pachychoroid MNV groups, respectively. Compared with the control group, cytokines were differently upregulated among the MNV groups. CRP and CXCL12 were significantly upregulated in all MNV groups, whereas CXCL13 and IL-8 were significantly upregulated in three MNV groups, excluding the non-pachychoroid/non-drusen-associated MNV group. Ang-2 was significantly upregulated in three MNV groups except the drusen-associated MNV group. PlGF was significantly upregulated in the pachychoroid-associated and drusen-associated MNV groups. CCL-2 was significantly upregulated in the pachychoroid-associated and pachychoroid/drusen-associated MNV groups. VEGF was downregulated in the pachychoroid-associated and drusen-associated MNV groups, respectively. Multidimensional scaling analysis showed a distinct cytokine profile for each MNV group. CONCLUSION: All MNV groups showed distinct cytokine profiles. Eyes with "neovascular age-related macular degeneration with drusen and concomitant pachychoroid" may share a similar etiology to those with "pachychoroid neovasculopathy" and "choroidal neovascularization with drusen," but have a distinct etiology to those without these. These findings suggest the importance of evaluating drusen and the choroid during the diagnosis of neovascular age-related macular degeneration.

Relationship between the vessel density around the optic nerve head and visual field deterioration in eyes with retinitis pigmentosa.

PURPOSE: To analyze the vessel density around the optic nerve head (ONH) by optical coherence tomography angiography (OCTA) in patients with retinitis pigmentosa (RP), and to evaluate its correlation with visual functions. METHODS: Thirty-eight eyes with RP with visual field constriction within the central 10° were enrolled. The mean (± SD) age of the patients was 43.7 ± 15.1 years. In addition to visual acuity (VA) measurements and visual field tests (Humphrey Field Analyzer 10-2 test), we also measured the vessel density at the macula by OCTA (superficial and deep vessel density: sVD(m) and dVD(m)) and in multiple layers around the ONH (vessel density in the radial peripapillary capillary [RPC] layer and in the nerve head [NH] layer: VDrpc and VDnh). The vessel density was calculated by binarizing the OCTA images. The associations between the logMAR VA and mean deviation (MD) values and the variables of central retinal thickness (CRT), sVD(m), dVD(m), VDrpc, VDnh, and also the size of the foveal avascular zone were investigated. RESULTS: The mean logMAR VA was 0.16 ± 0.34 and the MD value was - 17.2 ± 10.3 dB; the MD value was significantly related to the logMAR VA (p = 0.0028). Multivariate analysis with AICc model selection suggested only dVD(m) was associated with logMAR VA. On the other hand, the optimal model for the MD value included the CRT, dVD(m), and VDnh. CONCLUSION: The vessel density in the deep layer around the ONH was significantly associated with the visual field deterioration in patients with RP.

EVALUATION OF THE RETINAL HAZARD WITH 3D DIGITALLY ASSISTED VISUALIZATION SYSTEM AND CONVENTIONAL MICROSCOPE IN MACULAR SURGERIES.

PURPOSE: To investigate the retinal light hazard during macular surgery using a digital three-dimensional visualization system (3D) and a conventional microscope (CM). DESIGN: Experimental study and retrospective evaluation of a case-control study. SUBJECTS: A total of 20 and 10 patients who underwent pars plana vitrectomy for epiretinal membrane using 3D and CM, respectively. METHODS: Spectral irradiances of endoilluminators were measured for representative settings used during core vitrectomy and macular manipulations with 3D and CM. From the medical record of the patients, time needed for core vitrectomy and macular manipulations was extracted. The total retinal light hazard index and the macular hazard index were calculated based on the spectral irradiances weighted by the standard functions. Total retinal light hazard index, macular hazard index, and the number of cases that exceeded the maximum permissible radiant power exposure were compared between the two groups. RESULTS: The spectral irradiance were 1.6 and 3.9 mW/cm 2 for core vitrectomy and 3.4 and 8.1 mW/cm 2 for macular manipulations using typical settings for 3D and CM groups, respectively. The total retinal light hazard index ranged from 4.31 kJ/m 2 to 17.37 kJ/m 2 for 3D and 11.09 kJ/m 2 to 27.70 kJ/m 2 for CM groups, respectively, whereas the macular hazard index ranged from 2.93 kJ/m 2 to 14.58 kJ/m 2 for 3D and from 6.84 kJ/m 2 to 23.55 kJ/m 2 for CM, respectively ( P < 0.001). One (5%) and 6 (60%) pars plana vitrectomy cases exceeded the threshold limits with 3D and CM groups, respectively ( P < 0.05, chi-square test). CONCLUSION: The 3D digitally assisted visualization system offers significantly safer macular surgery compared with the CM, considering the potential retinal hazard.

HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid.

High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg­33% (20/60) and wild-type (WT)­7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.

Pachychoroid: current concepts on clinical features and pathogenesis.

PURPOSE: The term "pachychoroid" refers to a newly described phenotype in which functional and structural choroidal changes are thought to play a key pathogenic role in a spectrum of related retinal disorders. A more detailed understanding of how the choroid is involved within this spectrum and a better knowledge of the most relevant clinical signs of the pachychoroid phenotype are important to differentiate these disorders from other retinal conditions. Our objectives are to provide a literature review of pachychoroid and the commonalities that may be present across pathologies included in the spectrum, and to provide details on the examination, monitoring, and management of these disorders. METHODS: We searched the PubMed web platform to identify relevant studies using the following keywords: pachychoroid, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome, vasculopathy pachysclera, pachychoroid geographic atrophy, and pachydrusen. We selected 157 publications and identified the most important features related to pachychoroid. RESULTS: The presence of hypertrophic or congested vessels in the choroid, not thickened choroid per se, under an area of reduced or absent choriocapillaris in the posterior pole seems to be the most salient feature of pachychoroid. However, other qualitative/quantitative features are needed to differentiate the uncomplicated pachychoroid from the pathological pachychoroid clinical spectrum, which may be associated with exudation, neovascularization, and/or retinal pigment epithelium and photoreceptor atrophy. CONCLUSIONS: The most salient feature of pachychoroid appears to be the presence of large vessels under an area of reduced or absent choriocapillaris. Knowledge of the features and pathogenesis of the different disorders in the pachychoroid spectrum may assist in the management of patients.

Prevalence and Pattern of Geographic Atrophy in Asia: The Asian Eye Epidemiology Consortium.

PURPOSE: Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). DESIGN: Cross-sectional meta-analyses. PARTICIPANTS: A total of 97 213 individuals aged 40 years and older. METHODS: Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. MAIN OUTCOME MEASURES: Prevalence of GA per 1000 persons. RESULTS: The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04-2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97-6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07-0.62) to 2.90 per 1000 persons (95% CI, 1.55-4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22-3.23) and rural residents (1.33; 95% CI, 0.70-1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72-5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31-1.22, P = 0.005). CONCLUSIONS: Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

COMPARISON OF MULTICOLOR IMAGING AND COLOR FUNDUS PHOTOGRAPHY IN THE DETECTION OF PATHOLOGICAL FINDINGS IN EYES WITH POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To compare the appearance and frequency of detection of common features in eyes with polypoidal choroidal vasculopathy using multicolor imaging (MC) or color fundus photography (CFP). METHODS: Thirty-eight eyes with indocyanine green angiography-proven polypoidal choroidal vasculopathy, imaged with both MC and CFP, were graded by three independent retinal specialists. The presence of five prespecified pathological features (blood, exudation, polypoidal lesions, pigment epithelial detachments, and atrophy) was graded on each modality independently. Multimodal imaging including optical coherence tomography, fluorescein, and indocyanine green angiography was used as the gold standard. RESULTS: Overall, there was no statistically significant difference in the ability of MC imaging compared with CFP in detecting the pathological features. Polypoidal lesions appear as small, dark green, round lesions which have higher contrast on MC compared with a nodular orange appearance seen on CFP. Polypoidal lesions can be identified noninvasively using both MC and CFP in about half of the cases. CONCLUSION: There are differences in the appearance of polypoidal choroidal vasculopathy-associated features on MC compared with CFP. Both modalities are comparable for the detection of pathological features in eyes with polypoidal choroidal vasculopathy. MC imaging may be considered as an alternative to CFP.

IMPROVED DETECTION AND DIAGNOSIS OF POLYPOIDAL CHOROIDAL VASCULOPATHY USING A COMBINATION OF OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess the ability of optical coherence tomography (OCT) alone and in combination with OCT angiography (OCTA) to differentiate polypoidal choroidal vasculopathy (PCV) from neovascular age-related macular degeneration, as compared to fluorescein angiography and indocyanine green angiography. METHODS: This is a cross-sectional study. All participants had a standardized history, clinical examination including measurement of best-corrected visual acuity, slit-lamp biomicroscopy, and indirect fundus examination, and underwent standardized imaging (color photography, fluorescein and indocyanine green angiography, OCT, and OCTA) after predefined protocols. We used a 2-step approach (Step 1: spectral domain OCT; Step 2: addition of OCTA) combining structural OCT and OCTA to differentiate 50 treatment-naive eyes with PCV, choroidal neovascularization, and retinal angiomatous proliferation and compared with the diagnosis based on fluorescein angiography and indocyanine green angiography. Spectral domain OCT signs used to diagnose PCV included presence of two out of three of any retinal pigment epithelium detachment (pigment epithelial detachment/double-layer sign), notched or narrow-peaked pigment epithelial detachment, or round subretinal pigment epithelium structure. Optical coherence tomography angiography signs used to diagnose PCV included presence of a localized subretinal pigment epithelium hyperflow signal in the cross-sectional OCTA and/or presence of a focal hyperflow sign in en face OCTA based on outer retina slab. RESULTS: Based on fluorescein angiography and indocyanine green angiography, the diagnosis was choroidal neovascularization in 24 eyes, PCV in 23 eyes, and retinal angiomatous proliferation in 3 eyes. Based on spectral domain OCT signs, PCV was diagnosed in 19/23 (82.6%) eyes; however, specificity of OCT was only 51.9%. Cross-sectional OCTA showed a diffuse hyperflow signal in all 24 (100.0%) eyes with choroidal neovascularization, whereas a localized subretinal pigment epithelium hyperflow signal was detected in 19/23 (82.6%) eyes with PCV. En face OCTA only detected a nodular hyperflow signal in 10/23 eyes (43.5%) with PCV. Combination of OCT and OCTA achieved 82.6% sensitivity and 100.0% specificity for differentiating PCV from choroidal neovascularization/retinal angiomatous proliferation. CONCLUSION: Cross-sectional OCTA is more sensitive than en face OCTA in detecting flow signal in polyps. Combination of structural OCT and OCTA can be used to screen for PCV with a high level of sensitivity and specificity.

Low-frequency coding variants in CETP and CFB are associated with susceptibility of exudative age-related macular degeneration in the Japanese population.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analysed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method. We used a total of 2,886 (1st: 827, 2nd: 2,059) exudative AMD cases including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation and 9,337 (1st: 3,247 2nd: 6,090) controls. Gene-based analysis found a significant association of low-frequency variants (minor allele frequency (MAF) < 0.05) in CETP, C2 and CFB. The association of CETP remained after conditioned with all known genome-wide association study (GWAS) associated variants. In addition, when we included only disruptive variants, enrichment of rare variants (MAF < 0.01) was also observed after conditioned with all GWAS associated variants (P = 1.03 × 10−6, odds ratio (OR) = 2.48). Haplotype and conditional analysis of the C2-CFB-SKIV2L locus showed a low-frequency variant (R74H) in CFB would be individually associated with AMD susceptibility independent of the GWAS associated SNP. These findings highlight the importance of target sequencing to reveal the impact of rare or low-frequency coding variants on disease susceptibility in different ethnic populations.

Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration.

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.

COMPARISON OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHIC CHANGES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY ALONE OR IN COMBINATION WITH PHOTODYNAMIC THERAPY IN POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To compare changes in optical coherence tomography angiography in eyes with polypoidal choroidal vasculopathy after treatment with anti-vascular endothelial growth factor monotherapy or combined with photodynamic therapy. METHODS: This is a longitudinal case-controlled study. The authors performed optical coherence tomography angiography at baseline and Month 3 in patients with treatment-naive polypoidal choroidal vasculopathy undergoing monotherapy (n = 10) or combination therapy (n = 13). We analyzed flow signal within the outer retina and choriocapillaris using automated segmentation. The authors analyzed the presence of pachyvessels using a 10.4-µm segment through Haller layer. The changes in each layer were compared between treatments. RESULTS: At Month 3, both groups showed similar improvement in best-corrected visual acuity and central retinal thickness. However, flow signal within the polypoidal choroidal vasculopathy complex was decreased in more eyes after combination therapy than after monotherapy (84.6% vs. 40.0%, P = 0.04). Patchy reduction in flow signal within the choriocapillaris layer was noted in 15.4% and 10.0% after combination therapy and monotherapy, respectively (P = 0.61). Significant reduction in pachyvessel caliber was seen only after combination therapy but not after monotherapy (75.0% vs. 0.0%, P = 0.01). CONCLUSION: Longitudinal optical coherence tomography angiography demonstrates more significant reduction in lesion flow and pachyvessels in the short term after combination therapy than after monotherapy, although visual and structural OCT showed similar improvement.