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PURPOSE To assess the diagnostic accuracy of optical coherence tomography angiography (OCTA) compared with multimodal imaging for choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC) eyes and to determine the features that predicted CNV. DESIGN Prospective cross-sectional study. METHODS Consecutive CSC patients were recruited from retina clinic. The reference standard for CNV was determined by interpretation of multimodal imaging with OCTA, structural OCT line scan, fluorescein angiography (FA), indocyanine green angiography (ICGA), ultra-widefield fundus photography and fundus autofluorescence (FAF). Two independent masked graders examined OCTA without FA and ICGA to diagnose CNV. Univariate and multivariate analyses were performed to evaluate factors associated with CNV. RESULTS CNV was detected in 69 eyes in 64 out of 277 CSC patients according to reference standard. The two masked graders who examined OCTA had sensitivity of 81.2% (95% Confidence Interval [CI], 71.9%-90.4%) and 78.3% (95% CI, 68.5%-88.0%), specificity of 97.3% (95% CI, 95.9%-98.8%) and 96.2% (95% CI, 94.5%-98.0%), positive predictive values of 82.4% (95% CI, 73.3%-91.4%) and 76.1% (95% CI, 66.1%-86.0%), and negative predictive values of 97.1% (95% CI, 95.6%-98.7%) and 96.7% (95% CI, 95.0%-98.3%). Their mean area under the receiver operating characteristic curve (AUC) was 0.88 with good agreement (Kappa coefficient 0.80 [95% CI, 0.72-0.89]). Flat irregular pigment epithelial detachment on structural OCT, neovascular network on OCTA and ill-defined late leakage on FA significantly correlated with CNV in CSC from multiple regression (P CONCLUSIONS There is discordance between OCTA and multimodal imaging in diagnosing CNV in CSC. This study demonstrated the caveats in OCTA interpretation, such as small extrafoveal lesions and retinal pigment epithelial alterations. Comprehensive interpretation of OCTA with dye angiography and structural OCT is recommended.

Background/aimsTo determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections.MethodsThis is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid.ResultsThe presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness.Conclusion and relevanceBaseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.

Purpose To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV), and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiograph (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photograph findings. Design Evaluation of diagnostic test Participants Panel of retina specialists. Methods As part of the Asia-Pacific Ocular Imaging Society (APOIS), an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV and proposed an updated consensus nomenclature, which reflects our latest understanding based on imaging and histology reports. The workgroup evaluated a set of diagnostic features based on OCT and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria which does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. Main Outcome Measures A consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. Results The workgroup recommended the terms ‘polypoidal lesion’ and ‘branching neovascular network’ for the two key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based ‘major criteria’ (sub-RPE ring-like lesion, enface OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 110 eyes achieved an accuracy of 82%. Conclusions We propose updated terminology for PCV lesion components which better reflect the nature of these lesions which was based on international consensus. A set of practical diagnostic criteria that are easily applied to SD-OCT can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not routinely performed.

PURPOSE To provide a concise overview for ophthalmologists and practicing retina specialists of available clinical evidence of manipulating the angiopoietin/tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains (Tie) pathway and its potential as a therapeutic target in retinal vascular diseases. METHODS A literature search for articles on the angiopoietin/Tie pathway and molecules targeting this pathway that have reached Phase 2 or 3 trials was undertaken on PubMed, Association for Research in Vision and Ophthalmology meeting abstracts (2014-2019), and ClinicalTrials.gov databases. Additional information on identified pipeline drugs was obtained from publicly available information on company websites. RESULTS The PubMed and Association for Research in Vision and Ophthalmology meeting abstract search yielded 462 results, of which 251 publications not relevant to the scope of the review were excluded. Of the 141 trials related to the angiopoietin/Tie pathway on ClinicalTrials.gov, seven trials focusing on diseases covered in this review were selected. Vision/anatomic outcomes from key clinical trials on molecules targeting the angiopoietin/Tie pathway in patients with retinal vascular diseases are discussed. CONCLUSION Initial clinical evidence suggests a potential benefit of targeting the angiopoietin/Tie pathway and vascular endothelial growth factor-A over anti-vascular endothelial growth factor-A monotherapy alone, in part due to of the synergistic nature of the pathways.

Myopic choroidal neovascularization (CNV) is one of the most vision-threatening complications in patients with pathologic myopia. Over the last decade, anti-angiogenesis therapy with anti-vascular endothelial growth factor (anti-VEGF) agents has become the standard-of-care treatment for myopic CNV and ranibizumab has been approved for treating myopic CNV.Review of preclinical studies and clinical trials data supporting the use of ranibizumab for myopic CNV. Discussion on the mechanisms, efficacy, safety, regulatory affairs, and future directions of ranibizumab for myopic CNV are highlighted.Ranibizumab has demonstrated good efficacy and safety profile in multiple clinical trials and long-term studies for treating myopic CNV. Cost-effective analysis has shown that ranibizumab therapy is a cost-effective treatment for myopic CNV. Among the currently available anti-VEGF agents, ranibizumab is the only drug that is approved for the treatment of myopic CNV by the US Food and Drug Administration. In the coming few years, biosimilars of ranibizumab may become available and will have the potential to lower the cost of ranibizumab. Long-term visual gain after ranibizumab treatment for myopic CNV is limited by chorioretinal atrophy associated with pathologic myopia and further research is required to tackle the development of chorioretinal atrophy.

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.

Polypoidal choroidal vasculopathy (PCV) is a condition characterized by multiple, recurrent, serosanguineous pigment epithelial detachments, and neurosensory retinal detachments due to abnormal aneurysmal neovascular lesions. It is generally considered as a variant of neovascular age-related macular degeneration, but there are some differences between the clinical presentation, natural history, and treatment response between patients with PCV and typical neovascular age-related macular degeneration patients. Over the past decade, new research and technological advancements have greatly improved our understanding of the PCV disease process and the management of PCV. This review aims to summarize the recent research findings to highlight the epidemiology, pathogenesis, genetics, the application of various diagnostic tools for PCV, and the available treatment options for PCV.

PurposeThe endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis.MethodsThis study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed.ResultsTwo SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities.ConclusionThis study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.

Purpose: Review and provide consensus recommendations on use of treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) management with relevance for clinicians in the Asia-Pacific region. Methods: A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstract databases of the Asia-Pacific Vitreo-retina Society, European Society of Retina Specialists, American Academy of Ophthalmology, and Controversies in Ophthalmology: Asia-Australia congresses, was conducted to assess evidence for T&E regimens in nAMD. Only studies with ≥100 study eyes were included. An expert panel reviewed the results and key factors potentially influencing the use of T&E regimens in nAMD and PCV, and subsequently formed consensus recommendations for their application in the Asia-Pacific region. Results: Twenty-seven studies were included. Studies demonstrated that T&E regimens with aflibercept, ranibizumab, or bevacizumab in nAMD, and with aflibercept in PCV, were efficacious and safe. The recommendation for T&E is, after ≥3 consecutive monthly loading doses, treatment intervals can be extended by 2 to 4 weeks up to 12 to 16 weeks. When disease activity recurs, the recommendation is to reinject and shorten intervals by 2 to 4 weeks until fluid resolution, after which treatment intervals can again be extended. Intraretinal fluid should be treated until resolved; however, persistent minimal subretinal fluid after consecutive treatments may be tolerated with treatment intervals maintained or extended if the clinical condition is stable. Conclusions: T&E regimens are efficacious and safe for nAMD and PCV, can reduce the number of visits, and minimize the overall burden for clinicians and patients.

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p &lt, 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters, p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

Anti-angiogenesis therapy with intravitreal anti-VEGF agents is now the standard-of-care treatment for myopic choroidal neovascularization (CNV).We provide a critical review of the safety of all the anti-VEGF agents currently used for treating myopic CNV including ranibizumab, aflibercept, conbercept, bevacizumab, and ziv-aflibercept.Anti-VEGF therapy for myopic CNV with the currently available anti-VEGF drugs generally have favorable safety outcomes in the short-term. Nonetheless, ocular adverse events following anti-VEGF therapy for myopic CNV may develop and these include worsening or new development of myopic traction maculopathy, increased risk of retinal detachment, and progression of chorioretinal atrophy. Clinicians should be aware of these potential complications and evaluate them before and after anti-VEGF therapy.

The choriocapillaris plays a considerable role in the normal physiology of the eye as well as in various diseases. Assessing the changes in the choriocapillaris can therefore provide important information about normal ageing and pathogenesis of visual impairment, and even some systemic diseases. In vivo imaging of the choriocapillaris has evolved from non-depth resolved, dye-based angiography to advanced, high resolution optical coherence tomography angiography (OCTA). However, the intricate microvascular networks within the choriocapillaris are still beyond the resolving limits of most OCTA instruments. Knowledge of histology, meticulous image acquisition methods, recognition of artifact and post-acquisition processing techniques are necessary for optimizing OCTA choriocapillaris images. Qualitative and quantitative analyses of the choriocapillaris provide clinical information in age-related macular degeneration (AMD), diabetic retinopathy (DR), pathologic myopia and central serous chorioretinopathy (CSC). Furthermore, studies have revealed choriocapillaris changes in posterior uveitis that are correlated with treatment outcome and have important prognostic significance. In addition to retinal diseases, choriocapillaris changes have been observed in systemic vascular diseases and complications associated with pregnancy. This article is protected by copyright. All rights reserved.

PURPOSE To evaluate the efficacy and safety of 2 dosing regimens of ranibizumab 0.5 mg versus verteporfin photodynamic therapy in Asian patients with visual impairment due to myopic choroidal neovascularization. METHODS Eligible patients (aged ≥18 years) were randomized 2:2:1 to Group I (n = 182; ranibizumab treatment guided by visual acuity stabilization criteria); Group II (n = 184; ranibizumab treatment guided by disease activity); or Group III (n = 91; verteporfin photodynamic therapy on Day 1; from Month 3, ranibizumab/verteporfin photodynamic therapy/both treatment guided by disease activity). RESULTS The mean average best-corrected visual acuity change from baseline to Month 1 through Month 3 was significantly higher in Groups I/II versus Group III (Group I/II: +9.5/+9.8 letters vs. Group III: +4.5 letters; both P < 0.001). Group II was statistically noninferior to Group I for the mean average best-corrected visual acuity change from baseline to Month 1 through Month 6 (10.7 vs. 10.4 letters; P < 0.001). Over 12 months, the mean number of ranibizumab injections received by Groups I/II/III was 4.6/3.9/3.2. CONCLUSION In Asian patients, ranibizumab treatments demonstrated superior efficacy versus verteporfin photodynamic therapy at Month 3, and the beneficial treatment effects persisted at Month 12. Ranibizumab was well-tolerated and demonstrated a good safety profile.

Antivascular endothelial growth factor (anti-VEGF) agents are a safe and effective treatment option for neovascular age-related macular degeneration (nAMD). However, undertreatment related to the costs and route of administration of anti-VEGF agents remains a common problem for nAMD patients. The treat-and-extend (T&E) regimen for nAMD has proven to balance clinical effectivity with reduced numbers of injections. However, implementation of the T&E regimen depends on the capacity and resources of clinics and patient compliance. To determine the optimal T&E regimen for Hong Kong, a panel of retina specialists was initiated by MediPaper Medical Communications Limited to discuss the benefits and hurdles in adopting the T&E regimen and to develop recommendations for patient selection based on clinical needs, dosing criteria, and dosing regimen. Key recommendations included selecting patients with only-eye or recurrence for the T&E regimen, pre-booking clinic appointments to reduce patient visits, communicating the T&E regimen with non-vitreoretinal physicians and trainees, extending the maximum dose interval to 16 weeks, and actively engaging patients in decision making.

Background To determine the long-term prognosis of lamellar macular holes (LMH) in highly myopic eyes. Methods This was a retrospective observational study. Patients with LMH associated with high myopia (>-6 dioptres) were examined at regular 6-month intervals for a minimum of 36 months to detect for any structural and functional deterioration. Assessment included visual acuity checking, fundal examination, and optical coherence tomography (OCT) scanning. The risk factors for visual deterioration and progression to full-thickness macular hole (MH) were analysed using Kaplan-Meier survival analysis. The main outcome measures included the changes in mean best-corrected visual acuities, evidence of lamellar hole progression on OCT scans and complication rates of full-thickness macular hole (FTMH), and foveal detachment (FD) development. Results A total of 37 highly myopic eyes with optical coherence tomography confirmed LMH were recruited from 36 patients. The mean age was 63.4 ± 9.8 years and the mean spherical equivalent refractive error was − 9.01 ± 3.6 D with axial length of 27.74 ± 1.45 mm. The mean follow-up duration was 57.6 ± 10.9 months. The mean baseline visual acuity was 0.272 logMAR ± 0.22. A gradual decline in visual acuity was noted, and the change reached statistical significance from 36 months onwards. Visual acuity was 0.648 ± 0.41 logMAR at 36 months (p = 0.034) and 0.604 ± 0.455 at 48 months (p = 0.046). Twelve eyes (32.4%) had foveoschisis at baseline. Coexistence of a lamellar macular hole with foveoschisis was shown to be a risk factor for the development of a FTMH or FD (p = 0.002). Conclusion LMH in highly myopic eyes was generally stable, while a small proportion of patients progressed to full-thickness MH. Patients with coexisting LMH, foveoschisis, and vitreomacular traction had a higher risk of visual decline and progression to full-thickness MH.

PurposeTo develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti–vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment.DesignClinical study evaluating diagnostic accuracy.ParticipantsPatients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments.MethodsIn phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN).Main Outcome MeasuresSensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA.ResultsIn eyes with persistent activity, the combination of 3 non–ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN.ConclusionsIn nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL.

The proposed doses of chloroquine (CQ) and hydroxychloroquine (HCQ) for treatment of COVID-19 (1000 mg/day for 10 days, CQ; 800 mg first day then 400 mg/day for 5 days, HCQ) in many guidelines worldwide, are considerably higher than the maximum recommended daily safe doses of both agents (≤2.3 mg/kg/day, CQ; ≤5.0 mg/kg/day, HCQ) for development of retinal toxicity. Irreversible retinal damage can occur if the exposure to the safe doses is >5 years. It is not known whether exposure to high doses over a short period of time can also cause the damage. We recommend that before prescribing CQ or HCQ, history of ocular disease should be obtained to avoid the prescription if appropriate. If either agent is to be used, routine baseline ocular examination is not absolutely necessary. Patients who do not have ocular disease should also be informed about the potential risk of retinal toxicity. Both agents, however, have not yet been proven to be beneficial to COVID-19.

Polypoidal choroidal vasculopathy (PCV) is a serosanguinous maculopathy more frequently affecting Asian populations (Cheung et al. 2018). It was first described in the 1980s and is characterized by the presence of polyp-like aneurysmal subretinal vascular lesions which are best visualized using indocyanine green angiography (ICGA) (Yannuzzi et al. 1990). PCV is generally considered a subtype of age-related macular degeneration (AMD) as they share many common clinical features and risk factors (Wong et al. 2016). Yet, more recent evidence has demonstrated some significant disparities between PCV and typical AMD, particularly in their clinical course and response to treatment. Clinicians and researchers are now therefore considering PCV as a separate disease entity in its own right or as a variant of type 1 (sub-retinal pigment epithelial) choroidal neovascularization (CNV).

Purpose To assess the 1-year effectiveness, safety, and treatment patterns of ranibizumab in patients with myopic choroidal neovascularization (mCNV) enrolled in the LUMINOUS study. Methods This 5-year, prospective, multicenter, observational, study enrolled 30,138 patients across all approved ranibizumab indications from outpatient ophthalmology clinics. 297 consenting patients (≥18 years) with mCNV who were treatment-naive or prior-treated with ranibizumab or other ocular treatments were enrolled, and treated with ranibizumab according to the local product label. The main outcomes are visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters or equivalent), adverse events during the study, and treatment exposure over 1 year. Results are presented by prior treatment status of the study eye and injection frequency. Results Of the 297 mCNV patients recruited in the study, 108 were treatment-naive and 175 were prior ranibizumab-treated. At baseline, the mean age of patients was 57.6 years, and 59.0 years and 80.6% and 65.7% were female in the treatment-naive and prior ranibizumab-treated groups, respectively. Most were Caucasian (treatment-naive, 88.9%; prior ranibizumab-treated, 86.9%). The mean (±standard deviation [SD]) VA letter changes to 1 year were +9.7 (±17.99) from 49.5 (±20.51) and +1.5 (±13.15) from 58.5 (±19.79) and these were achieved with a mean (SD) of 3.0 (±1.58) and 2.6 (±2.33) injections in the treatment-naive and prior ranibizumab-treated groups, respectively. Presented by injection frequencies 1–2, 3–4 and ≥5 injections in Year 1, the mean (SD) VA changes were +15.0 (±14.70), +7.7 (±19.91) and −0.7 (±16.05) in treatment-naive patients and +1.5 (±14.57), +3.1 (±11.53) and −3.6 (±11.97) in prior ranibizumab-treated patients, respectively. The safety profile was comparable with previous ranibizumab studies. Conclusions Ranibizumab treatment for mCNV showed robust VA gains in treatment-naive patients and VA maintenance in prior ranibizumab-treated patients in a clinical practice setting, consisting mainly of Caucasians. No new safety signals were observed during the study.

Background: Diabetic macular edema (DME) is the primary cause of irreversible vision loss among individuals with diabetes mellitus (DM). We developed, validated, and tested a deep-learning (DL) system for classifying DME using images from three common commercially available optical coherence tomography (OCT) devices. Methods: We trained and validated two versions of a multi-task network to classify DME (centre-involved DME [CI-DME], non-CI-DME, or absence of DME) using three-dimensional (3D) volume-scans and two-dimensional (2D) B-scans respectively. A total of 73,746 OCT images were used for training and primary validation. External testing was performed using 26,981 images across seven independent datasets from Singapore, Hong Kong, the US, China, and Australia. Findings: In classifying the presence or absence of DME, the DL system achieved area under the receiver operating characteristic curves (AUROCs) of 0.937 (95% CI 0.920–0.954), 0.958 (0.930–0.977), and 0.965 (0.948–0.977) for primary datasets obtained from Cirrus, Spectralis, and Triton OCTs respectively, in addition to AUROCs greater than 0.906 for the external datasets. For the further classification of the CI-DME and non-CI-DME subgroups, the AUROCs were 0.968 (0.940–0.995), 0.951 (0.898–0.982), and 0.975 (0.947–0.991) for the primary datasets and greater than 0.894 for the external datasets. Interpretation: We demonstrated excellent performance with a DL system for the automated classification of DME, highlighting its potential as a promising second-line screening tool for patients with DM, which will create a more effective triaging mechanism to tertiary eye clinics. Funding: Research Grants Council General Research Fund, Hong Kong; Research to Prevent Blindness; and National Institutes of Health Grant. Conflict of Interest: We report no potential conflicts of interest relevant to this article. Ethical Approval: The current study presented here was conducted in accordance with the 1964 Declaration of Helsinki and was approved by local research ethics committees. Because the study is a retrospective analysis of fully anonymized OCT images, the ethics committees waived the requirements for informed consent.

Fluorescein angiography and indocyanine green angiographies are investigations commonly performed for the evaluation of retinal and choroidal vascular circulatory changes. This chapter provides an overview on the principles of fluorescein and indocyanine green angiographies and describe their applications in the assessment of various retinal diseases and how they can be used in the preoperative or postoperative evaluation of macular surgery.

Myopic choroidal neovascularization (CNV) is a major complication in patients with pathologic myopia, often resulting in metamorphopsia and central visual loss due to the photoreceptor damage and development of macular chorioretinal atrophy around the regressed CNV. Myopic CNV often affects younger age groups and the long-term outcomes of untreated myopic CNV are generally poor. Various therapeutic options such as thermal focal laser photocoagulation and verteporfin photodynamic therapy (vPDT) have been explored in the treatment of myopic CNV, but many of these modalities have produced suboptimal long-term visual outcomes. Clinical trials like the VIP Study have demonstrated the efficacy of vPDT in stabilizing vision in patients with myopic CNV in the short term, but there was visual deterioration after vPDT in longer-term follow-up. Vascular endothelial growth factor (VEGF) is one of the main angiogenic factors implicated in the development of CNV including myopic CNV. In recent years, major randomized controlled clinical trials have been conducted to evaluate the efficacy and safety of intravitreal anti-VEGF therapy. These include REPAIR, RADIANCE, and BRILLIANCE studies on ranibizumab; MYRROR study on aflibercept; and SHINY study on conbercept. Results from these major clinical trials have demonstrated intravitreal anti-VEGF therapy to be efficacious and safe in the treatment of myopic CNV, producing promising visual and anatomical outcomes. This chapter will summarize the study designs and key findings of these key clinical trials on myopic CNV.

A retrospective cohort study of East-Asian patients previously treated with ranibizumab for myopic choroidal neovascularization in the RADIANCE trial. Clinical charts were reviewed to assess long-term efficacy and safety. Visual acuity was sustained for additional 36 months after trial completion with few patients requiring additional treatment and no new safety concerns observed., Purpose: To evaluate long-term efficacy and safety of ranibizumab for treatment of myopic choroidal neovascularization (mCNV) in clinical practice. Methods: Noninterventional, retrospective cohort study of East-Asian patients previously treated with ranibizumab during the RADIANCE trial. Forty-one patients who completed the RADIANCE trial were followed-up for up to 48 months (post-RADIANCE observation period). Outcome measures were best-corrected visual acuity changes from baseline (assessed at RADIANCE trial initiation), mCNV recurrences, and ocular adverse events. Results: Mean visual gain from baseline best-corrected visual acuity (56.5 ± 12.1 letters) (20/80) was significant at 12 months (+14.3 ± 11.4 letters, n = 40, P < 0.0001), 24 months (+10.4 ± 22.3 letters, n = 31, P = 0.0143), 30 months (+11.0 ± 22.4 letters, n = 29, P = 0.0134), 42 months (+12.9 ± 20.9 letters, n = 25, P = 0.0051), and 48 months (+16.3 ± 18.7, n = 16, P = 0.0034). Of the 16 patients who completed 48 months of follow-up, 63% gained ≥10 letters and 13% lost ≥10 letters. Over the post-RADIANCE observation period, 83% of patients required no further treatment for mCNV, 10% experienced mCNV recurrences, and 12% experienced a nonserious ocular adverse event. Patients who required additional treatment for mCNV received a mean of 5.0 (SD 5.9, range 1.0–18.0) ranibizumab injections. Conclusion: Best-corrected visual acuity gained at the end of the RADIANCE trial was sustained over additional 36 months of follow-up. Few patients required further treatment and no new safety concerns were observed.

Purpose To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration. Design A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study. Participants One hundred seventy-eight eligible patients aged ≥18 years. Methods Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). Main Outcome Measures Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months. Results Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from >5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab. Conclusions The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a >1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, ranibizumab was well tolerated with no new safety findings up to month 12.

Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration (AMD) subtype and is seen particularly in Asians. Previous studies have suggested disparity in response to intravitreal injections of anti–vascular endothelial growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred treatment for PCV has remained unclear. Recent research has provided novel insights into the pathogenesis of PCV, and imaging studies based on OCT suggest that PCV belongs to a spectrum of conditions characterized by pachychoroid, in which disturbance in the choroidal circulation seems to be central to its pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV. Importantly, 2 large, multicenter randomized clinical trials evaluating the safety and efficacy of anti-VEGF monotherapy and combination with photodynamic therapy (PDT) recently reported initial first-year outcomes, providing level I evidence to guide clinicians in choosing the most appropriate therapy for PCV. In this review, we summarize the latest updates in the epidemiologic features, pathogenesis, and advances in imaging and treatment trials, with a focus on the most recent key clinical trials. Finally, we propose current management guidelines and recommendations to help clinicians manage patients with PCV. Remaining gaps in current understanding of PCV, such as significance of polyp closure, high recurrence rate, and heterogeneity within PCV, are highlighted where further research is needed.

Danny Siu-Chun Ng,1 Zihan Sun,1 Alvin Lerrmann Young,1,2 Simon Tak-Chuen Ko,3 Jerry Ka-Hing Lok,1 Timothy Yuk-Yau Lai,1 Shameema Sikder,4 Clement C Tham1 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, 2Department of Ophthalmology, Prince of Wales Hospital, 3Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong, People’s Republic of China; 4Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA Objective: To identify residents’ perceived barriers to learning phacoemulsification surgical procedures and to evaluate whether virtual reality simulation training changed these perceptions. Design: The ophthalmology residents undertook a simulation phacoemulsification course and proficiency assessment on the Eyesi system using the previously validated training modules of intracapsular navigation, anti-tremor, capsulorrhexis, and cracking/chopping. A cross-sectional, multicenter survey on the perceived difficulties in performing phacoemulsification tasks on patients, based on the validated International Council of Ophthalmology’s Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR), using a 5-point Likert scale (1 = least and 5 = most difficulty), was conducted among residents with or without prior simulation training. Mann–Whitney U tests were carried out to compare the mean scores, and multivariate regression analyses were performed to evaluate the association of lower scores with the following potential predictors: 1) higher level trainee, 2) can complete phacoemulsification most of the time (>90%) without supervisor’s intervention, and 3) prior simulation training. Setting: The study was conducted in ophthalmology residency training programs in five regional hospitals in Hong Kong. Results: Of the 22 residents, 19 responded (86.3%), of which 13 (68.4%) had completed simulation training. Nucleus cracking/chopping was ranked highest in difficulty by all respondents followed by capsulorrhexis completion and nucleus rotation/manipulation. Respondents with prior simulation training had significantly lower difficulty scores on these three tasks (nucleus cracking/chopping 3.85 vs 4.75, P = 0.03; capsulorrhexis completion 3.31 vs 4.40, P = 0.02; and nucleus rotation/manipulation 3.00 vs 4.75, P = 0.01). In multivariate analyses, simulation training was significantly associated with lower difficulty scores on these three tasks. Conclusion: Residents who had completed Eyesi simulation training had higher confidence in performing the most difficult tasks perceived during phacoemulsification. Keywords: virtual reality, simulation surgical education, cataract surgery

Purpose To describe intravitreal ranibizumab treatment frequency, clinical monitoring, and visual outcomes (including mean central retinal thickness [CRT] and visual acuity [VA] changes from baseline) in neovascular age-related macular degeneration (nAMD) in real-world settings across three ranibizumab reimbursement scenarios in the Middle East, North Africa, and the Asia–Pacific region. Methods Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed. Results More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of −0.7 letters and a decrease in CRT of −44.4 μm. The greatest mean CRT change was observed in the self-paid group, with −92.6 μm. Conclusions UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity. Electronic supplementary material The online version of this article (10.1007/s00417-017-3890-8) contains supplementary material, which is available to authorized users.

Pathologic myopia is a leading cause of visual impairment. Development of myopic choroidal neovascularization (CNV) is one of the most common complications that leads to central vision loss in patients with pathologic myopia. If left untreated, it can cause scarring with expanding macular atrophy leading to irreversible visual loss in a period as short as 5 years. Advancements in multimodal imaging technology have furthered our understanding of the condition; however, further studies are necessary to extend its utility in the diagnosis of myopic CNV. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has become the standard-of-care and the recommended first-line treatment option for myopic CNV. Long-term studies have demonstrated that early treatment of confirmed myopic CNV cases with an intravitreal anti-VEGF agent is useful to avoid late-stage complications. This strategy has also been shown to achieve visual outcome improvements for up to 4 years and visual stabilization up to 6 years. This review article provides an overview of the current knowledge on myopic CNV and discusses recent updates in the diagnosis and management of the condition. Furthermore, treatment recommendations are provided based on the authors' expert opinions.

Age-related macular degeneration (AMD) is one of the leading causes of severe vision loss in people over 60 years. Wet AMD (wAMD) causes more severe visual acuity (VA) loss compared with the dry form due to formation of choroidal neovascularization (CNV). Antivascular endothelial growth factor (anti-VEGF) agents such as ranibizumab and aflibercept are now the standard of care treatment for wAMD. Unfortunately, up to a quarter of anti-VEGF-treated wAMD patients might not fully benefit from intravitreal injections and CNV activity may not respond to the treatment and these patients are called anti-VEGF nonresponders. This article aims to discuss the baseline factors associated with VA outcome such as age, initial VA, lesion types, disease duration, optical coherence tomography (OCT) features, fundus autofluorescence findings, and the presence of particular genotype risk alleles in patients with wAMD. Recommendations are provided regarding when to consider discontinuation of therapy because of either success or futility. Understanding the predictive factors associated with VA outcome and treatment frequency response to anti-VEGF therapy may help retina specialists to manage patients’ expectations and guide treatment decisions from the beginning of treatment on the basis of “personalized medicine.”

Topic The aim of this article is to review and compile available information on the classification, pathophysiology, and clinical features of myopic choroidal neovascularization (CNV); to describe the latest data on the management of this disease; and to present guidance. Clinical Relevance In the United States, myopia affects approximately 34 million people (2010), and similar figures have been reported in Europe. Pathologic myopia (PM), a possible consequence of myopia, is estimated to affect up to 3% of the global population. One of the most serious complications of PM is myopic CNV, which often leads to a sudden onset but progressive decline in central vision and is associated with a poor prognosis unless treated. Furthermore, 35% of patients with myopic CNV develop bilateral disease in the fellow eye within 8 years. Although intravitreal anti–vascular endothelial growth factor (VEGF) therapies have had a major impact on the management of patients with myopic CNV, there remain significant gaps in our understanding of this condition and how to best administer treatment. Additionally, the long-term safety and efficacy of these treatments are largely unknown. Methods We carried out a literature review (September 2015) of all English-language articles in PubMed resulting from searches of the following terms: "choroidal neovascularization" AND "myopia" OR "myopic macular degeneration" OR "degenerative myopia" OR "myopic maculopathy" OR "myopic retinopathy" OR "pathological myopia" OR "pathologic myopia." Results We screened a total of 566 abstracts, and 250 articles were deemed relevant for full publication review. We excluded a further 71, but an additional 44 articles were identified. This resulted in 223 articles being used to develop this review. Conclusions Highly myopic patients experiencing a sudden loss of central vision should be referred for further examination. Once a diagnosis of myopic CNV has been confirmed, after fluorescein angiography, treatment initiation should be prompt and anti-VEGF agents considered as first-line therapy, unless contraindicated. Continued monitoring of patients is required to assess any progression or recurrence of the condition.

Diabetic macular oedema is the most common cause of diabetic retinopathy-induced vision loss. Efficacy of anti-vascular endothelial growth factor therapy in diabetic macular oedema has been demonstrated in randomized controlled trials. An Asian-specific guideline for diabetic macular oedema treatment is needed as patients in Asia tend to present with far more advanced disease than seen elsewhere in the world. Previous reviews of diabetic macular oedema management lacked a broader assessment of anti-vascular endothelial growth factor treatment choices and newer trials. Recent clinical trial data allow head-to-head comparisons between the different anti-vascular endothelial growth factor agents and treatment regimens. This review aims to summarize the clinical evidence related to various treatment regimens for clinicians, with a focus on anti-vascular endothelial growth factor therapies, and to provide guidance on the treatment of diabetic macular oedema in Asian patients.

Purpose: To evaluate the fundus autofluorescence (FAF) findings in eyes with acute zonal occult outer retinopathy (AZOOR) and the relationships between the FAF, spectral-domain optical coherence tomography (SD-OCT), and Humphrey visual field (HVF) findings. Methods: We performed a retrospective review of the clinical features and FAF, SD-OCT, and HVF findings of 23 eyes of 22 consecutive patients with AZOOR. The mean deviation (MD) values of HVF were compared between areas of normal and abnormal FAF. Results: FAF abnormalities were detected in 21 (91.3%) eyes, with diffuse hyperautofluorescence in 19 (82.6%) eyes and mottling autofluorescence in 2 (8.7%) eyes. In all eyes with FAF abnormality, a clear boundary between the affected and unaffected retina was observed. SD-OCT revealed loss of ellipsoid zone in retinal regions corresponding to the dysfunctional areas demonstrated by HVF. The FAF abnormality also corresponded with the boundaries demonstrated by SD-OCT and/or HVF. The differences in HVF MD values between areas with normal and abnormal FAF in AZOOR eyes were significantly higher than in normal unaffected eyes (p < 0.05). Conclusions: FAF abnormalities were detected in most AZOOR eyes, and the former corresponded to the abnormal retinal regions revealed by SD-OCT and HVF. The findings suggested that FAF is a useful investigation for the assessment of AZOOR.

BackgroundNeovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are sight-threatening maculopathies with both environmental and genetic risk factors. We have previously shown relative risks posed by genes of the complement pathways to neovascular AMD and PCV.MethodsIn this study, we investigated the haplotype-tagging single nucleotide polymorphisms (SNPs) in thecomplement component 5(C5) gene in 708 unrelated Chinese individuals: 200 neovascular AMD patients, 233 PCV patients and 275 controls. Six tagging SNPs inC5were genotyped. Univariate single SNP association analysis, haplotype-based association analysis and gene-gene interaction analysis betweenC5and other AMD-associated genes were performed.ResultsThe results revealed none of the six tagging SNPs of theC5gene had a significant association with neovascular AMD or PCV (P > 0.05). We also found insignificant haplotype-based association, and no significant SNP-SNP interaction betweenC5and other genes (includingC2-CFB-RDBP-SKIV2L,SERPING1,CETP,ABCG1,PGF,ANGPT2,CFHandHTRA1) for neovascular AMD and PCV.ConclusionsThis study showed no statistical significance in the genetic association ofC5with neovascular AMD or PCV in a Hong Kong Chinese population. Further studies in large samples from different populations are warranted to elucidate the role ofC5in the genetic susceptibility of AMD and PCV.

Contains fulltext : 215584.pdf (Publisher’s version ) (Open Access) Central serous chorioretinopathy (CSC) is a common cause of central vision loss, primarily affecting men 20-60 years of age. To date, no consensus has been reached regarding the classification of CSC, and a wide variety of interventions have been proposed, reflecting the controversy associated with treating this disease. The recent publication of appropriately powered randomised controlled trials such as the PLACE trial, as well as large retrospective, non-randomised treatment studies regarding the treatment of CSC suggest the feasibility of a more evidence-based approach when considering treatment options. The aim of this review is to provide a comprehensive overview of the current rationale and evidence with respect to the variety of interventions available for treating CSC, including pharmacology, laser treatment, and photodynamic therapy. In addition, we describe the complexity of CSC, the challenges associated with treating CSC, and currently ongoing studies. Many treatment strategies such as photodynamic therapy using verteporfin, oral mineralocorticoid antagonists, and micropulse laser treatment have been reported as being effective. Currently, however, the available evidence suggests that half-dose (or half-fluence) photodynamic therapy should be the treatment of choice in chronic CSC, whereas observation may be the preferred approach in acute CSC. Nevertheless, exceptions can be considered based upon patient-specific characteristics.

Supplemental Digital Content is Available in the Text. Twelve-month results from LUMINOUS support the use of ranibizumab as an effective first-line therapy for polypoidal choroidal vasculopathy. Higher baseline visual acuity and adequate injection frequency were associated with better visual acuity outcomes. No new safety signals were identified., Purpose: To evaluate the real-world effectiveness and safety of intravitreal ranibizumab 0.5 mg in treatment-naive patients with and without polypoidal choroidal vasculopathy (PCV). Methods: Assessment of neovascular age-related macular degeneration patients with or without PCV after 12 months of ranibizumab treatment during the LUMINOUS study. Outcome measures were visual acuity and central retinal thickness changes from baseline and the rate of ocular adverse events. Results: At baseline, 572 and 5,644 patients were diagnosed with and without PCV, respectively. The mean visual acuity gain from baseline at Month 12 in the PCV and non-PCV groups was +5.0 and +3.0 letters, respectively; these gains were achieved with a mean of 4.4 and 5.1 ranibizumab injections. Eighty percent of PCV patients and 72.2% of non-PCV patients who had baseline visual acuity ≥73 letters maintained this level of vision at Month 12; 20.6% and 17.9% of patients with baseline visual acuity

Purpose To report the clinical outcomes of adalimumab in treating refractory Behcet’s disease (BD)-related uveitis in paediatric or adolescent patients. Methods Retrospective review of five paediatric or adolescent patients with BD-related uveitis with a minimum follow-up of 24 months. Results Disease quiescence was observed in 9 (90%) of 10 eyes at 12 months. The mean number of relapses per year per patient was 5 (range, 3–7) before initiation of adalimumab treatment. This was reduced to 0.2 relapse per patient per year among the five patients during the first 24 months after starting adalimumab treatment. At baseline, 5 eyes had active retinal vasculitis. Retinal vasculitis resolved in all cases (100%) after starting adalimumab. The mean time to complete resolution of inflammation was 3.4 weeks. The mean ± standard deviation logMAR best-corrected visual acuity was 0.711 ± 0.63 at baseline and improved to 0.172 ± 1.04 at 12 months (P < 0.001). None of the patients developed any adverse events associated with adalimumab treatment. Conclusion Adalimumab was effective in preventing irreversible sight-threatening BD-related uveitis in paediatric or adolescent patients. Adalimumab appears to be a promising treatment option for young patients with recalcitrant BD-related uveitis and has a favourable safety profile.

Background:Choroidal neovascularization (CNV) in adults is most commonly associated with neovascular age-related macular degeneration (AMD) and pathologic myopia. Though less common, CNV can also develop from other conditions such as uveitis, central serous chorioretinopathy, angioid streaks, intraocular tumors, hereditary chorioretinal dystrophies, or can be idiopathic in origin. If left untreated, CNV may cause visual loss because of exudation of intraretinal or subretinal fluid, retinal or subretinal hemorrhage, or fibrosis involving the macula. It is well known that one of the main drivers of angiogenesis in CNV development is vascular endothelial growth factor (VEGF) and therefore inhibitors of VEGF might be an effective treatment for CNV.Methods:The goal of this review is to provide an overview and summary in the use of pharmacotherapy especially anti-VEGF therapy, in the treatment of CNV due to uncommon causes.Results:Results from uncontrolled case series and controlled clinical trials have reported good efficacy and safety in using anti-VEGF agents including bevacizumab, ranibizumab, aflibercept and ziv-aflibercept in the treatment of CNV due to uncommon causes. Anti-VEGF has also been used in combination with verteporfin PDT and anti-inflammatory agents for treating CNV of various causes.Conclusion:Pharmacotherapy with anti-VEGF agents is an effective treatment option for CNV due to uncommon etiologies.

Pathologic myopia is a major cause of visual impairment worldwide. Pathologic myopia is distinctly different from high myopia. High myopia is a high degree of myopic refractive error, whereas pathologic myopia is defined by a presence of typical complications in the fundus (posterior staphyloma or myopic maculopathy equal to or more serious than diffuse choroidal atrophy). Pathologic myopia often occurs in eyes with high myopia, however its complications especially posterior staphyloma can also occur in eyes without high myopia. Owing to a recent advance in ocular imaging, an objective and accurate diagnosis of pathologic myopia has become possible. Especially, optical coherence tomography has revealed novel lesions like dome-shaped macula and myopic traction maculopathy. Wide-field optical coherence tomography has succeeded in visualizing the entire extent of large staphylomas. The effectiveness of new therapies for complications have been shown, such as anti-VEGF therapies for myopic macular neovascularization and vitreoretinal surgery for myopic traction maculopathy. Myopia, especially childhood myopia, has been increasing rapidly in the world. In parallel with an increase in myopia, the prevalence of high myopia has also been increasing. However, it remains unclear whether or not pathologic myopia will increase in parallel with an increase of myopia itself. In addition, it has remained unclear whether genes responsible for pathologic myopia are the same as those for myopia in general, or whether pathologic myopia is genetically different from other myopia.

A 23-year-old male with intermittent visual loss in his left eye for 4 months was originally treated as optic neuritis elsewhere. Upon presentation to our hospital (Beijing Tongren Hospital), his left eye visual acuity was reduced to hand motion at face. The left eye ocular motility was limited in upgaze, downgaze, adduction, and abduction. Computed tomography and magnetic resonance imaging revealed lesions in the sphenoid and ethmoid sinuses, orbital apex and carvernous sinus invading adjacent extraocular muscles. Endoscopic ethmo-sphenoidostomy and debulking surgery was performed and histopathology of the specimen demonstrated alveolar rhabdomyosarcoma. Despite having treatment with a combination of orbital radiation therapy and systemic chemotherapy, the patient developed generalized metastasis with cachexia and the left eye became no light perception due to optic atrophy.

To review and summarize the latest developments in the diagnosis and management of myopic choroidal neovascularization (mCNV).A review of the literature was performed, focusing on tests and investigations for diagnosing mCNV, as well as the key treatment options available for mCNV.Standard essential tests and investigations for diagnosing mCNV include spectral-domain optical coherence tomography for screening, fluorescein angiography for confirmation, and indocyanine green angiography and fundus autofluorescence for providing supplementary information. The current first line treatment of mCNV is the use of anti-vascular endothelial growth factor therapy.Various investigations can assist the differentiation of mCNV from other coexisting retinal pathologies associated with myopia or choroidal neovascularization resulting from other causes. Prompt use of anti-vascular endothelial growth factor therapy has good efficacy and safety in the treatment of mCNV.

Background The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. Pattern of Retinopathy Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. Dose We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight. Risk of Toxicity The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. Major Risk Factors High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. Screening Schedule A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. Screening Tests The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. Toxicity Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. Counseling Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening.

The natural course of high-axial myopia is variable and the development of pathologic myopia is not fully understood. Advancements in optical coherence tomography (OCT) technology have revealed peculiar intraocular structures in highly myopic eyes and unprecedented pathologies that cause visual impairment. New OCT findings include posterior precortical vitreous pocket and precursor stages of posterior vitreous detachment; peripapillary intrachoroidal cavitation; morphological patterns of scleral inner curvature and dome-shaped macula. Swept source OCT is capable of imaging deeper layers in the posterior pole for investigation of optic nerve pits, stretched and thinned lamina cribrosa, elongated dural attachment at posterior scleral canal, and enlargement of retrobulbar subarachnoid spaces. This has therefore enabled further evaluation of various visual field defects in high myopia and the pathogenesis of glaucomatous optic neuropathy. OCT has many potential clinical uses in managing visual impairing conditions in pathologic myopia. Understanding how retinal nerve fibers are redistributed in axial elongation will allow the development of auto-segmentation software for diagnosis and monitoring progression of glaucoma. OCT is indispensable in the diagnosis of various conditions associated with myopic traction maculopathy and monitoring of post-surgical outcomes. In addition, OCT is commonly used in the multimodal imaging assessment of myopic choroidal neovascularization. Biometry and topography of the retinal layers and choroid will soon be validated for the classification of myopic maculopathy for utilization in epidemiological studies as well as clinical trials.

The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P .001). Participants in the combination group received fewer ranibizumab injections (median, 6.0 [interquartile range (IQR), 4.0-11.0]) than the monotherapy group (median, 12.0 [IQR, 7.0-17.0]) up to month 24. The combination group required a median of 2.0 (IQR, 1.0-3.0) vPDT treatments for 24 months, with 75 of 168 participants (44.6%) requiring only 1 vPDT treatment.The 24-month data findings confirm that ranibizumab therapy, given as monotherapy or in combination with vPDT, is efficacious and safe for treatment of PCV. Combination therapy with vPDT added to ranibizumab achieved superior BCVA gain, increased odds of complete polypoidal lesion regression, and fewer treatment episodes compared with ranibizumab monotherapy.ClinicalTrials.gov Identifier: NCT01846273.

In the 12-month MINERVA study, a subgroup of 5 adolescent patients aged 13–17 years received open-label ranibizumab 0.5 mg at baseline, followed by individualized pro re nata regimen based on disease activity, for the treatment of choroidal neovascularization. Visual and anatomical outcomes were improved, and no new safety findings were observed with ranibizumab., Purpose: To evaluate the efficacy and safety of ranibizumab 0.5 mg in adolescent patients with any choroidal neovascularization etiology enrolled in the 12-month MINERVA study. Methods: In the open-label, non-randomized study arm, ranibizumab 0.5 mg was administered to five adolescents (aged 13–17 years). The findings were assessed descriptively as individual case reports at Month 12. Best-corrected visual acuity changes, central subfield thickness, treatment exposure, and safety were described over 12 months. Results: Baseline choroidal neovascularization etiologies of the study eye included choroidal neovascularization secondary to Best disease (n = 2), idiopathic chorioretinopathy (n = 2), and optic disk drusen (n = 1). At Months 2, 6, and 12, the observed mean best-corrected visual acuity changes in the study eye from baseline were +9.2, +16.6, and +16.6 letters, respectively, and the observed mean central subfield thickness change from baseline was −31.4, −87.6, and −116.4 μm, respectively. Adolescent patients received a mean of three (range, 2–5) ranibizumab injections in the study eye. No adverse events or serious adverse events related to ranibizumab were reported. Conclusion: Ranibizumab 0.5 mg treatment was beneficial in improving visual acuity and stabilizing or reducing central subfield thickness in five adolescents with differing choroidal neovascularization etiologies requiring infrequent injection. No new safety findings were observed over 12 months.

Background. To evaluate the treatment outcomes of patients with punctate inner choroidopathy (PIC) and secondary choroidal neovascularization (CNV). Methods. This is a retrospective study of 24 eyes in 22 patients suffering from PIC with CNV. Patients were treated with intravitreal ranibizumab monotherapy (14 eyes) or combined oral corticosteroid and intravitreal ranibizumab therapy (corticosteroid-ranibizumab group, 10 eyes). Mean follow-up duration was 24.0 months. We evaluated best-corrected visual acuity (BCVA), fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and optical coherence tomography, before and after treatment. The following variables were compared between groups: number of intravitreal ranibizumab injections, BCVA, recurrence of CNV, and change in PIC lesions. Results. The ranibizumab monotherapy group received an average of 3 intravitreal ranibizumab injections; mean logMAR visual acuity improvement was 0.34, and 8 eyes developed recurrent CNV during follow-up. The corticosteroid-ranibizumab group received an average of 1.9 intravitreal ranibizumab injections; mean logMAR visual acuity improvement was 0.61, and there was no recurrence of CNV. Combined corticosteroid-ranibizumab therapy also resulted in better resolution of PIC lesions and fewer new PIC lesions. Conclusion. Both corticosteroid-ranibizumab treatment and ranibizumab monotherapy could significantly improve the vision of PIC patients with CNV. Combined corticosteroid and intravitreal ranibizumab treatment appeared to reduce CNV recurrence and development of new PIC lesions compared with ranibizumab monotherapy.

Post hoc analyses of the Asian subpopulation of the VIEW trials demonstrated that visual and anatomic outcomes were similar in eyes treated with intravitreal aflibercept and ranibizumab, and were similar to outcomes seen in white patients., Purpose: To assess the treatment effect of intravitreal aflibercept and ranibizumab in Asian patients with neovascular age-related macular degeneration. Methods: We evaluated data from VIEW 1 and VIEW 2, comparing functional and morphologic outcomes at Week 96 between intravitreal aflibercept 2 mg monthly (2q4) or 2 mg bimonthly after 3 initial monthly doses (2q8) versus ranibizumab 0.5 mg monthly among Asian patients (n = 269) and between Asian and white patients (n = 2044). Results: In Asian patients, there were no significant differences between intravitreal aflibercept 2q4 and 2q8 compared with ranibizumab in mean gain in best-corrected visual acuity (10.23 and 8.35 vs. 8.51 letters). Reduction in central retinal thickness was greater for intravitreal aflibercept 2q4 (150.43 μm, P = 0.0075) and 2q8 (148.15 μm, P = 0.0126) than ranibizumab (119.46 μm). The proportion of dry retinas was greater for intravitreal aflibercept 2q4 (65.7%, P < 0.01) than ranibizumab (41.7%). There were no differences in outcomes between Asian and white patients. Serious treatment-emergent ocular adverse events occurred in