A case of secondary multiple evanescent white dot syndrome in a patient with preexisting wet age-related macular degeneration.

Purpose: To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration. Observation: A 75-year-old male on treat and extend regimen for wet age-related macular degeneration (AMD) presented with a sudden loss of vision and saw central dark shadow in the right eye (RE) for a duration of 1 week. There was no significant history preceding the visual loss. Examination showed a visual acuity (VA) of counting fingers at 1 meter in the right eye and 20/25 in the left eye. Anterior segment examination was unremarkable with dilated fundus examination showing a clear vitreous, tortuous blood vessel, a hyperemic disc and fibrosis at the macula. The left eye (LE) examination was unremarkable. Optical Coherence Tomography (OCT) showed fibrosis due to the previous wet AMD and hyperreflective excrescences projecting from the retinal pigment epithelium (RPE) outside of the old area of wet AMD. Fundus Fluorescein Angiogram (FFA) showed hyperfluorescent spots in a wreath-like pattern increasing in intensity in the early phase and showing late staining towards the late phase while Indocyanine green angiography (ICGA) did not clearly delineate the lesions. Fundus autofluorescence (FAF) revealed hyper Autofluorescence (AF) at the posterior pole. Optical Coherence Tomography Angiography (OCTA) revealed a flow reduction in the choriocapillaris of the affected area. Basic blood investigations with Venereal Disease Research Laboratory (VDRL), syphilitic IgM and IgG antibodies, Quantiferon TB gold test, complete renal function tests and liver function tests were performed. All the blood investigations were within normal limits and the workup for syphilis and tuberculosis was negative. The patient was started on 1mg/kg body weight of oral prednisolone (after the non-response to low dose of oral steroids) with the diagnosis of secondary multiple evanescent white dot syndrome (MEWDS) secondary to wet AMD. The patient was followed up every weekly and the last visit showed improvement in visual acuity to 20/50 with resolution of lesions on FAF and OCT macula. Conclusion and importance: Secondary MEWDS is extremely rare and unique in terms of its presentation and its association with preexisting chorioretinal disease where there is damage to the choriocapillaris- Bruch's membrane-RPE complex. This case report highlights one such rare case scenario and how multimodal imaging helps in the diagnosis, management and follow-up of patients with secondary MEWDS.

Polypoidal Choroidal Vasculopathy: Evaluation Based on 3-Dimensional Reconstruction of OCT Angiography.

OBJECTIVE: Three-dimensional (3D) reconstruction using swept-source OCT angiography (SS-OCTA) can provide insights into the nature and structure of polypoidal choroidal vasculopathy (PCV) and its component parts, the polypoidal lesion (PL) and the branching neovascular network (BNN). This study aims to describe novel observations of PCV using 3D reconstruction of SS-OCTA, and to compare these observations with similar images of type I macular neovascularization (MNV) typical neovascular age-related macular degeneration (nAMD). DESIGN: Clinical case series. SUBJECTS: Patients with PCV in either eye from clinical studies conducted in a tertiary retina center. METHODS: Images with prespecified SS-OCTA imaging protocol were obtained and reconstructed in 3D. Forty neovascularization lesions (30 PCV and 10 typical nAMD) based on SS-OCTA were analyzed. MAIN OUTCOME MEASURES: The following 3 specific features were evaluated: (1) the pattern of flow signal within the PLs as either homogenous or showing internal vascular architecture; (2) the configuration of the BNN as hypermature, mature, or immature; and (3) the spatial arrangement of the PLs in relation to the BNN. Comparisons were made between PCV and typical nAMD. RESULTS: All PLs exhibited internal vascular architecture in the form of coil-like loops and none exhibited homogenous flow. Small focal nodules were present within this internal vascular architecture in 70% of PLs. Branching neovascular networks exhibited a hypermature/mature configuration (100 vs. 50%, P < 0.01) and were associated with thicker choroid compared with typical nAMD type 1 MNV (238.7 ± 104.3 vs. 155.6 ± 49.2, P = 0.02). The BNN and PL were located at distinct anteroposterior planes in 81% of the eyes. CONCLUSIONS: We identified proliferating vasculature in both the PL and the BNN. Comparison of the configuration suggests that the BNN represents a more chronic and inactive lesion than the PL. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Features Associated With Vision in Eyes With Subfoveal Fibrosis From Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the characteristics and correlation of visual acuity in eyes treated for neovascular age-related macular degeneration (nAMD) and developed fibrosis. DESIGN: Case-control study. METHODS: Three hundred fifty-six treatment-naive nAMD eyes that were treated for 12 months were included. Fibrosis was defined as present if well-defined hyperreflective material (HRM) were present between the neurosensory retina and the Bruch membrane on optical coherence tomography (OCT) that correlated with well-defined regions of yellowish pallor on fundus photography and/or staining on fluorescence angiography. OCT features of subfoveal fibrosis and the overlying retina were correlated with visual acuity at month 12. RESULTS: Sixty-three eyes (20.3%) developed incident fibrosis at month 12. Compared with eyes that did not develop fibrosis, these eyes had lower baseline vision (49 vs 54 letters, P = .02) and more of them had type 2 macular neovascularization (15.0 vs 8.8%, P = .03), larger lesion area (29.6 vs 15.1 mm2, P = .02), and subretinal hemorrhage ≥4 disc diameters (44.4% vs 19.8%, P < .01). Visual acuity was worse in the incident fibrosis compared with the group that never developed fibrosis by month 12. (-1.4±17.1 versus +6.0±17.4 letters, P < .01). In 83 eyes that had subfoveal fibrosis, better vision was associated with intact ellipsoid zone-external limiting membrane complex (ß coefficient 29.4, 95% CI 14.2-44.6, P < .01), whereas worse vision was associated with retinal pigment epithelium (RPE)-involving HRM, HRM above the RPE, and width of HRM (ß coefficients -25.4 [95% CI -36.3 to -14.6], P < .01; -23.5 [95% CI -39.0 to -7.9], P < .01; and -3.8 [95% CI -7.2 to -0.4], P = .03, respectively). CONCLUSION: Although fibrosis is associated with poorer visual outcome, preservation of external limiting membrane and level of fibrosis relative to the RPE are associated with visual outcomes.

The economic burden of inherited retinal disease in Singapore: a prevalence-based cost-of-illness study.

OBJECTIVE: To assess the economic impact of inherited retinal disease (IRD) among Singaporeans. METHODS: IRD prevalence was calculated using population-based data. Focused surveys were conducted for sequentially enrolled IRD patients from a tertiary hospital. The IRD cohort was compared to the age- and gender-matched general population. Economic costs were expanded to the national IRD population to estimate productivity and healthcare costs. RESULTS: National IRD caseload was 5202 cases (95% CI, 1734-11273). IRD patients (n = 95) had similar employment rates to the general population (67.4% vs. 70.7%; p = 0.479). Annual income was lower among IRD patients than the general population (SGD 19,500 vs. 27,161; p < 0.0001). Employed IRD patients had lower median income than the general population (SGD 39,000 vs. 52,650; p < 0.0001). Per capita cost of IRD was SGD 9382, with a national burden of SGD 48.8 million per year. Male gender (beta of SGD 6543, p = 0.003) and earlier onset (beta of SGD 150/year, p = 0.009) predicted productivity loss. Treatment of the most economically impacted 10% of IRD patients with an effective IRD therapy required initial treatment cost of less than SGD 250,000 (USD 188,000) for cost savings to be achieved within 20 years. CONCLUSIONS: Employment rates among Singaporean IRD patients were the same as the general population, but patient income was significantly lower. Economic losses were driven in part by male patients with early age of onset. Direct healthcare costs contributed relatively little to the financial burden.

Joint Multimodal Deep Learning-based Automatic Segmentation of Indocyanine Green Angiography and OCT Images for Assessment of Polypoidal Choroidal Vasculopathy Biomarkers.

Purpose: To develop a fully-automatic hybrid algorithm to jointly segment and quantify biomarkers of polypoidal choroidal vasculopathy (PCV) on indocyanine green angiography (ICGA) and spectral domain-OCT (SD-OCT) images. Design: Evaluation of diagnostic test or technology. Participants: Seventy-two participants with PCV enrolled in clinical studies at Singapore National Eye Center. Methods: The dataset consisted of 2-dimensional (2-D) ICGA and 3-dimensional (3-D) SD-OCT images which were spatially registered and manually segmented by clinicians. A deep learning-based hybrid algorithm called PCV-Net was developed for automatic joint segmentation of biomarkers. The PCV-Net consisted of a 2-D segmentation branch for ICGA and 3-D segmentation branch for SD-OCT. We developed fusion attention modules to connect the 2-D and 3-D branches for effective use of the spatial correspondence between the imaging modalities by sharing learned features. We also used self-supervised pretraining and ensembling to further enhance the performance of the algorithm without the need for additional datasets. We compared the proposed PCV-Net to several alternative model variants. Main Outcome Measures: The PCV-Net was evaluated based on the Dice similarity coefficient (DSC) of the segmentations and the Pearson's correlation and absolute difference of the clinical measurements obtained from the segmentations. Manual grading was used as the gold standard. Results: The PCV-Net showed good performance compared to manual grading and alternative model variants based on both quantitative and qualitative analyses. Compared to the baseline variant, PCV-Net improved the DSC by 0.04 to 0.43 across the different biomarkers, increased the correlations, and decreased the absolute differences of clinical measurements of interest. Specifically, the largest average (mean ± standard error) DSC improvement was for intraretinal fluid, from 0.02 ± 0.00 (baseline variant) to 0.45 ± 0.06 (PCV-Net). In general, improving trends were observed across the model variants as more technical specifications were added, demonstrating the importance of each aspect of the proposed method. Conclusion: The PCV-Net has the potential to aid clinicians in disease assessment and research to improve clinical understanding and management of PCV. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Update on Retinal Vein Occlusion.

Retinal vein occlusion represents the second leading cause of retinal vascular disorders, with a uniform sex distribution worldwide. A thorough evaluation of cardiovascular risk factors is required to correct possible comorbidities. The diagnosis and management of retinal vein occlusion have changed tremendously in the last 30 years, but the assessment of retinal ischemia at baseline and during follow-up examinations remains crucial. New imaging techniques have shed light on the pathophysiology of the disease and laser treatment, once the only therapeutic option, is now only one of the possible approaches with antivascular endothelial growth factors and steroid injections being preferred in most cases. Nowadays long-term outcomes are better than those achievable 20 years ago and yet, many new therapeutic options are under development, including new intravitreal drugs and gene therapy. Despite this, some cases still develop sight-threatening complications deserving a more aggressive (sometimes surgical) approach. The purpose of this comprehensive review is to reappraise some old but still valid concepts and to integrate them with new research and clinical data. The work will provide an overview of the disease's pathophysiology, natural history, and clinical features along with a detailed discussion on the advantages of multimodal imaging and of the different treatment strategies with the aim of providing retina specialists with the most updated knowledge in the field.

Genetic Variability of Complement Factor H Has Ethnicity-Specific Associations With Choroidal Thickness.

Purpose: To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort. Methods: A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort. Results: A total of 1045 healthy Asian individuals (550 Chinese, 147 Indians, 348 Malays) were prospectively enrolled in the study. Several CFH alleles (rs800292, rs1061170, and rs1329428) were associated with increased SFCT in Indians (+18.7 to +31.7 µm; P = 0.001-0.038) and marginally associated with decreased SFCT in Malays (-12.7 to -20.6 µm; P = 0.014-0.022). Haplotype analysis of CFH revealed variable associations with SFCT among races, with the H6 haplotype being associated with a 29.08-µm reduction in SFCT in the Chinese cohort (P = 0.02) but a 35.2-µm increase in SFCT in the Indian cohort (P < 0.001). Finally, subfield analysis of the Chinese cohort identified associations between the CFH risk allele rs1061170 and reduced CT in the nasal and superior sectors (-20.2 to -25.8 µm; P = 0.003-0.027). Conclusions: CFH variants are variably associated with CT among Asian ethnic groups. This has broad implications for the pathogenesis of common diseases such as age-related macular degeneration and central serous choroidopathy, the pathogenesis of which is associated with CT.

Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration.

Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.

Polypoidal Choroidal Vasculopathy: Updates on Risk Factors, Diagnosis, and Treatments.

There have been recent advances in basic research and clinical studies in polypoidal choroidal vasculopathy (PCV). A recent, large-scale, population-based study found systemic factors, such as male gender and smoking, were associated with PCV, and a recent systematic review reported plasma C-reactive protein, a systemic biomarker, was associated with PCV. Growing evidence points to an association between pachydrusen, recently proposed extracellular deposits associated with the thick choroid, and the risk of development of PCV. Many recent studies on diagnosis of PCV have focused on applying criteria from noninvasive multimodal retinal imaging without requirement of indocyanine green angiography. There have been attempts to develop deep learning models, a recent subset of artificial intelligence, for detecting PCV from different types of retinal imaging modality. Some of these deep learning models were found to have high performance when they were trained and tested on color retinal images with corresponding images from optical coherence tomography. The treatment of PCV is either a combination therapy using verteporfin photodynamic therapy and anti-vascular endothelial growth factor (VEGF), or anti-VEGF monotherapy, often used with a treat-and-extend regimen. New anti-VEGF agents may provide more durable treatment with similar efficacy, compared with existing anti-VEGF agents. It is not known if they can induce greater closure of polypoidal lesions, in which case, combination therapy may still be a mainstay. Recent evidence supports long-term follow-up of patients with PCV after treatment for early detection of recurrence, particularly in patients with incomplete closure of polypoidal lesions.

Geographic Atrophy Phenotypes in Subjects of Different Ethnicity: Asia-Pacific Ocular Imaging Society Work Group Report 3.

OBJECTIVE: To characterize geographic atrophy (GA) and evaluate differences between Asians and non-Asians. DESIGN: Multicenter, retrospective case series. PARTICIPANTS: Subjects aged ≥ 50 years with GA secondary to age-related macular degeneration in the absence of neovascularization in the study eye and follow-up of ≥ 2 years. METHODS: The GA lesion characterized at baseline and last follow-up based on multimodal imaging (fundus autofluorescence [FAF], near infrared [NIR], and spectral domain-OCT). Patients were grouped as either Asian or non-Asian. MAIN OUTCOME MEASURES: Comparison of (1) phenotypes of GA lesions (size, foveal involvement, number of foci, drusen background, and choroid background) and (2) growth rates of GA. RESULTS: A total of 144 patients (169 eyes) with distribution of 50.9% Asians and 49.1% non-Asians. The age and sex were similar between Asians and non-Asians (Asians: mean age, 77.2 ± 10.1 years, 47.9% female; non-Asians: mean age, 79.7 ± 8.4 years, 58.7% female). Asians exhibited thicker choroids (167 ± 74 versus [vs.] 134 ± 56 µm; P < 0.01) and lower prevalence of drusen (40.7% vs. 66.3%; P < 0.01). At baseline, the GA area was smaller in Asians vs. non-Asians (NIR, 3.7 ± 4.6 vs. 6.3 ± 6.8 mm2; P = 0.01: FAF, 2.4 ± 3.4 vs. 8.4 ± 9.6 mm2; P < 0.01). Asians had fewer GA foci (1.7 ± 1.3 vs. 2.7 ± 2.2; P < 0.01) compared to non-Asians. The proportion with diffused or banded FAF junctional zone pattern was similar between Asians and non-Asians (44.2% vs. 60.2%; P = 0.20). Asians had a slower GA lesion growth rate than non-Asians (NIR, 0.7 vs. 1.9 mm2/year; P < 0.01: FAF, 0.3 vs. 2.0 mm2/year; P < 0.01: NIR, 0.2 vs. 0.4 mm/year; P < 0.01 square root transformed: FAF, 0.1 vs. 0.3 mm/year; P < 0.01 square root transformed). The factors associated with GA lesion growth rate are (from the highest effect size) ethnicity, junctional zone FAF pattern, baseline GA area, and number of GA foci. Higher GA lesion growth rate was observed in both Asian and non-Asian subgroups, with drusen or lesion size and FAF patterns meeting inclusion criteria of recent therapeutic trials, but growth rate remained significantly slower in Asians. Eyes with baseline lesion ≥ 5 mm2 showed the highest growth rate, and the difference between ethnicities was no longer significant (2.6 vs. 3.3 mm2/year; P = 0.14). CONCLUSIONS: There are differences in GA lesion phenotype, associated features, and growth rate between Asians and non-Asian subjects. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Longer treatment intervals are associated with reduced treatment persistence in neovascular age related macular degeneration.

AIMS: To test the hypothesis that patients treated for neovascular age related macular degeneration (nAMD) with longer treatment intervals are more likely to persist with treatment. METHODS: Data were obtained from the prospectively-defined Fight Retinal Blindness! registry. Treatment interval at 2 years was stratified based on the mean treatment interval over the three visits prior to and including the 2-year visit. Rates of non-persistence to follow-up were assessed from 2 to 5 years. RESULTS: Data from 1538 eyes were included. The overall rate of non-persistence was 51% at 5 years. Patients on longer treatment intervals (12-weeks) at 2 years were found to be less persistent to long-term follow-up. These eyes were found to have fewer active disease visits in the first 2 years (40%) than eyes treated at 4-weekly intervals (66%, p < 0.001). In the multivariable analysis, better vision at 2 years was associated with a lower risk of non-persistence (hazards ratio [HR] [95% CI]: 0.95 [0.93, 0.97], P < 0.001), while longer treatment intervals (HR [95% CI]: 1.31 [0.95, 1.8] and 1.54 [1.15, 2.06] for 12-week and > 12-week intervals vs. 4-week intervals, respectively, P = 0.002) and older patients (HR [95% CI]: 1.03 [1.02, 1.04], p < 0.001) were at higher risk of non-persistence. CONCLUSIONS: We found that patients on longer treatment intervals at 2 years were more likely to be non-persistent with treatment in later years. Reinforcing the need for ongoing treatment is important for patients on longer intervals who may feel complacent or that treatment is no longer effective, particularly if newer, longer lasting agents become widely available.

Identifying the content for an item bank and computerized adaptive testing system to measure the impact of age-related macular degeneration on health-related quality of life.

PURPOSE: We are developing an age-related macular degeneration (AMD) health-related quality of life (HRQoL) item bank, applicable to Western and Asian populations. We report primarily on content generation and refinement, but also compare the HRQoL issues reported in our study with Western studies and current AMD-HRQoL questionnaires. METHODS: In this cross-sectional, qualitative study of AMD patients attending the Singapore National Eye Centre (May-December 2019), items/domains were generated from: (1) AMD-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with AMD patients (n = 27); and (4) written feedback from retinal experts. Following thematic analysis, items were systematically refined to a minimally representative set and pre-tested using cognitive interviews with 16 AMD patients. RESULTS: Of the 27 patients (mean ± standard deviation age 67.9 ± 7.0; 59.2% male), 18 (66.7%), two (7.4%), and seven (25.9%) had no, early-intermediate, and late/advanced AMD (better eye), respectively. Whilst some HRQoL issues, e.g. activity limitation, mobility, lighting, and concerns were similarly reported by Western patients and covered by other questionnaires, others like anxiety about intravitreal injections, work tasks, and financial dependency were novel. Overall, 462 items within seven independent HRQoL domains were identified: Activity limitation, Lighting, Mobility, Emotional, Concerns, AMD management, and Work. Following item refinement, items were reduced to 219, with 31 items undergoing amendment. CONCLUSION: Our 7-domain, 219-item AMD-specific HRQoL instrument will undergo psychometric testing and calibration for computerized adaptive testing. The future instrument will enable users to precisely, rapidly, and comprehensively quantify the HRQoL impact of AMD and associated treatments, with item coverage relevant across several populations.

Evolving treatment paradigms for PCV.

Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular AMD (nAMD) that accounts for a significant proportion of nAMD cases worldwide, and particularly in Asia. Contemporary PCV treatment strategies have closely followed those used in typical nAMD, though there are significant gaps in knowledge on PCV management and it remains unclear if these strategies are appropriate. Current clinical trial data suggest intravitreal anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy is effective in managing haemorrhage and exudation in PCV, although the optimal treatment interval, including as-needed and treat-and-extend approaches, is unclear. Newer imaging modalities, including OCT angiography and high-resolution spectral domain OCT have enabled characterisation of unique PCV biomarkers that may provide guidance on how and when treatment and re-treatment should be initiated. Treatment burden for PCV is a major focus of future therapeutic research and several newly developed anti-VEGF agents, including brolucizumab, faricimab, and new modes of drug delivery like the port delivery system, offer hope for dramatically reduced treatment burden for PCV patients. Beyond anti-VEGF therapy, recent developments in our understanding of PCV pathophysiology, in particular the role of choroidal anatomy and lipid mediators in PCV pathogenesis, offer new treatment avenues that may become clinically relevant in the future. This article explores the current management of PCV and more recent approaches to PCV treatment based on an improved understanding of this unique disease process.

Real-world cost-effectiveness of anti-VEGF monotherapy and combination therapy for the treatment of polypoidal choroidal vasculopathy.

OBJECTIVES: For patients with polypoidal choroidal vasculopathy (PCV), intravitreal anti-vascular endothelial growth factor (anti-VEGF) combination therapy has been shown to be cost-saving relative to monotherapy in a clinical trial setting. However, whether this also applies to real-world settings is unclear. We aim to compare the real-world functional outcomes and cost-effectiveness of intravitreal anti-VEGF combination therapy relative to monotherapy, to investigate whether combination therapy is truly cost-saving. METHODS: We used a Markov model to simulate a hypothetical cohort of PCV patients treated at Singapore National Eye Centre. Model parameters were informed by coarsened exact matched estimates of a two-year retrospective study of patients who initiated treatment in 2015. Treatment options included intravitreal aflibercept, bevacizumab, or ranibizumab, as monotherapy or in combination with full-fluence verteporfin photodynamic therapy. RESULTS: The two-year logMAR letters gains were significant for combination therapy ( + 10.6, P = 0.006) but not monotherapy (-2.2, P = 0.459). Over 20 years, a PCV patient would cost the health system SGD 48,790 under monotherapy and SGD 61,020 under combination therapy. Quality-adjusted life-years (QALYs) were estimated to be 7.41 for monotherapy and 7.80 for combination therapy. The incremental cost-effectiveness ratio of combination therapy was SGD 31,460/QALY, which is less than the common willingness-to-pay threshold of per capita gross domestic product of Singapore (SGD 88,990/QALY). Sensitivity analysis showed that combination therapy remained incrementally cost-effective, but not cost-saving. CONCLUSIONS: Our study shows that combination therapy is good value for money but is likely to increase costs when applied in real-world settings.

Diabetic Macular Ischemia: Influence of Optical Coherence Tomography Angiography Parameters on Changes in Functional Outcomes Over One Year.

Purpose: To prospectively evaluate whether diabetic macular ischemia detected with coherence tomography angiography (OCTA) is associated with change in functional outcomes over a period of one year. Methods: This is a one-year prospective, observational study that included 56 eyes with varying levels of diabetic retinopathy. All participants underwent best corrected visual acuity evaluation, swept-source OCTA and microperimetry at baseline and repeated at one year. Parafoveal vessel densities (VD) and foveal avascular zone (FAZ) areas were generated from OCTA in the superficial and deep vascular plexuses. The influence of baseline and change in OCTA parameters on change in visual acuity and retinal sensitivity over one year was evaluated. Results: Over the one-year follow-up period, 16% (9) of eyes had at least one line worsening in BCVA and 7% (4) of eyes had at least 5% decrease in retinal sensitivity compared to baseline. Diabetic retinopathy progressed in 12.5%. Mean superficial vascular plexus (SVP) FAZ area increased (0.32 ± 0.15 to 0.39 ± 0.18 mm2, P = 0.003) and parafoveal VD in deep vascular plexus (DVP) decreased (49.8 ± 3.7% to 48.8 ± 2.9%, P = 0.040) at one year compared to baseline. In the multivariate regression analysis, larger baseline DVP FAZ area was associated with worsening of BCVA over one year (ß = 0.16 logMAR per mm2, 95% CI 0.02 to 0.31, P = 0.032). In addition, larger decreases in SVP VD (ß = -4.18 db per 10% decrease, 95% CI -6.55 to -1.80, P = 0.002) was associated with worsening of retinal sensitivity over one year. Conclusions: Progression of parafoveal microvasculature changes over one year can be detected using OCTA. Larger baseline DVP FAZ area on OCTA is predictive of worsening in visual outcomes, and larger decreases in SVP VD were associated with worsening of retinal sensitivity over a course of one year in diabetic individuals.

Gene-Based Therapeutics for Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber's congenital amaurosis due to RPE65 mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations. Emphasis is placed on five distinct approaches to gene-based therapy that have potential to treat the full spectrum of IRDs: 1) gene replacement using adeno-associated virus (AAV) and nonviral delivery vectors, 2) genome editing via the CRISPR/Cas9 system, 3) RNA editing by endogenous and exogenous ADAR, 4) mRNA targeting with antisense oligonucleotides for gene knockdown and splicing modification, and 5) optogenetic approaches that aim to replace the function of native retinal photoreceptors by engineering other retinal cell types to become capable of phototransduction.

DIABETIC MACULAR ISCHEMIA: Correlation of Retinal Vasculature Changes by Optical Coherence Tomography Angiography and Functional Deficit.

PURPOSE: To examine the relationship between macular microvasculature parameters and functional changes in persons with diabetic retinopathy (DR). METHODS: Cross-sectional study of 76 eyes with varying levels of DR. Optical coherence tomography angiography (OCTA) quantified superficial and deep perifoveal vessel densities and foveal avascular zone areas. Retinal sensitivity was measured using microperimetry. Optical coherence tomography angiography parameters and retinal sensitivity were correlated. RESULTS: Deep perifoveal vessel density decreased with increasing severity of DR (adjusted mean 51.93 vs. 49.89 vs. 47.96, P-trend = 0.005). Superficial and deep foveal avascular zone area increased with increasing DR severity (adjusted mean: 235.0 µm vs. 303.4 µm vs. 400.9 µm, P-trend = 0.003 [superficial]; 333.1 µm vs. 513.3 µm vs. 530.2 µm, P-trend = 0.001 [deep]). Retinal sensitivity decreased with increasing DR severity (adjusted mean: 25.12 dB vs. 22.34 dB vs. 20.67 dB, P-trend = 0.003). Retinal sensitivity correlated positively with deep perifoveal vessel density (Pearson's ρ = 0.276, P = 0.020) and inversely with superficial foveal avascular zone area (Pearson's ρ = -0.333, P = 0.010). CONCLUSION: Alterations in retinal microvasculature can be observed with OCTA with increasing severity of DR. These changes are correlated with reduced retinal sensitivity. Optical coherence tomography angiography is useful to detect and quantify the microvasculature properties of eyes with diabetic macular ischemia.

New Concepts in Polypoidal Choroidal Vasculopathy Imaging: A Focus on Optical Coherence Tomography and Optical Coherence Tomography Angiography.

Polypoidal choroidal vasculopathy (PCV) is a variant of neovascular age-related macular degeneration. It is characterized by polypoidal dilatations at the terminus of branching vascular network located beneath the retinal pigment epithelium. These polypoidal lesions are best visualized on indocyanine green angiography. With recent advances in ocular imaging, optical coherence tomography (OCT) and OCT angiography (OCTA) have been increasingly used to aid in the diagnosis and monitoring of treatment responses in PCV. This review provides a summary of the current status of various imaging modalities in PCV, with special focus on OCT and OCTA.