Highlights from the 2019 International Myopia Summit on 'controversies in myopia'.

Myopia is an emerging public health issue with potentially significant economic and social impact, especially in East Asia. However, many uncertainties about myopia and its clinical management remain. The International Myopia Summit workgroup was convened by the Singapore Eye Research Institute, the WHO Regional Office for the Western Pacific and the International Agency for the Prevention of Blindness in 2019. The aim of this workgroup was to summarise available evidence, identify gaps or unmet needs and provide consensus on future directions for clinical research in myopia. In this review, among the many 'controversies in myopia' discussed, we highlight three main areas of consensus. First, development of interventions for the prevention of axial elongation and pathologic myopia is needed, which may require a multifaceted approach targeting the Bruch's membrane, choroid and/or sclera. Second, clinical myopia management requires co-operation between optometrists and ophthalmologists to provide patients with holistic care and a tailored approach that balances risks and benefits of treatment by using optical and pharmacological interventions. Third, current diagnostic technologies to detect myopic complications may be improved through collaboration between clinicians, researchers and industry. There is an unmet need to develop new imaging modalities for both structural and functional analyses and to establish normative databases for myopic eyes. In conclusion, the workgroup's call to action advocated for a paradigm shift towards a collaborative approach in the holistic clinical management of myopia

The danger of wearing an anorak

Campaigns to reduce road traffic accidents have paid little attention to the way headgear could interfere with vision. Binocular visual field measurement was undertaken in six healthy volunteers wearing four different types of anorak. All four anoraks greatly reduced the horizontal and superior field of vision. The anorak producing the worst reduction resulted in a width of vision of 99° and only 15° of vision above eye level, versus 167° and 52° respectively without an anorak. Anorak wearers should turn their heads to look sideways before crossing the road

Potential for Treatment Interval Extension in Eyes with nAMD Disease Activity Post Loading Phase in HAWK and HARRIER

Abstract Introduction The HAWK and HARRIER studies evaluated the efficacy and safety of brolucizumab versus aflibercept in treatment-naïve eyes with neovascular age-related macular degeneration. Based on the study design, brolucizumab-treated eyes adjusted to a q8w regimen because the presence of disease activity (DA) at the end of the matched loading phase (Week 16) could not subsequently extend to a q12w interval. The aim of this post hoc analysis was to assess subsequent DA in this subgroup to determine the potential for interval extensions during the first year of treatment. Methods Pooled data from the brolucizumab 6 mg arms and aflibercept arms of HAWK and HARRIER were included. Presence of DA was determined by the masked investigator based on their assessment of functional and anatomical parameters measured by optical coherence tomography. DA was compared at DA assessments, conducted at Weeks 16, 20, 32, and 44; fluid was also assessed at the primary analysis at Week 48. Results Fewer brolucizumab- (22.8%) than aflibercept-treated (32.2%) eyes had DA at the first DA assessment at Week 16. In eyes with investigator-identified DA at Week 16, BCVA change from baseline to Week 96 was comparable between treatment arms. Fewer brolucizumab- than aflibercept-treated eyes had DA at each subsequent DA assessment in Year 1: 31.8% vs 39.1% (Week 20), 27.3% vs 43.5% (Week 32), and 17.3% vs 31.2% (Week 44). Fewer eyes treated with brolucizumab than aflibercept had intraretinal and/or subretinal fluid: 35.3% vs 43.5% (Week 20), 55.8% vs 69.6% (Week 32), 30.0% vs 43.1% (Week 44), and 48.6% vs 68.6% (Week 48). Conclusion These findings indicate that, in eyes that still had DA 8 weeks after the final dose of loading phase, brolucizumab-treated eyes had improved fluid resolution and higher potential for treatment interval extension than aflibercept-treated eyes during the first year of treatment

Real-world effectiveness and safety of ranibizumab for the treatment of myopic choroidal neovascularization: Results from the LUMINOUS study

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 ( 6518 years) with mCNV who were treatment-na\uefve 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-na\uefve 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-na\uefve and prior ranibizumab-treated groups, respectively. Most were Caucasian (treatment-na\uefve, 88.9%; prior ranibizumab-treated, 86.9%). The mean (\ub1standard deviation [SD]) VA letter changes to 1 year were +9.7 (\ub117.99) from 49.5 (\ub120.51) and +1.5 (\ub113.15) from 58.5 (\ub119.79) and these were achieved with a mean (SD) of 3.0 (\ub11.58) and 2.6 (\ub12.33) injections in the treatment-na\uefve and prior ranibizumab-treated groups, respectively. Presented by injection frequencies 1\u20132, 3\u20134 and 655 injections in Year 1, the mean (SD) VA changes were +15.0 (\ub114.70), +7.7 (\ub119.91) and 120.7 (\ub116.05) in treatment-na\uefve patients and +1.5 (\ub114.57), +3.1 (\ub111.53) and 123.6 (\ub111.97) 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-na\uefve 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

Myopic Choroidal Neovascularization: Review, Guidance, and Consensus Statement on Management.

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

Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases

Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A. Simultaneous VEGF-A and ANG-2 inhibition was found to reduce vessel lesion number, permeability, retinal edema, and neuron loss more effectively than either agent alone in a spontaneous choroidal neovascularization (CNV) model. We describe the generation of a bispecific domain-exchanged (crossed) monoclonal antibody (CrossMAb; RG7716) capable of binding, neutralizing, and depleting VEGF-A and ANG-2. RG7716 showed greater efficacy than anti-VEGF-A alone in a non-human primate laser-induced CNV model after intravitreal delivery. Modification of RG7716’s FcRn and FccR binding sites disabled the antibodies’ Fc-mediated effector functions. This resulted in increased systemic, but not ocular, clearance. These properties make RG7716 a potential nextgeneration therapy for neovascular indications of the eye

Clinical impact of the worldwide shortage of verteporfin (Visudyne®) on ophthalmic care

INTRODUCTION: Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. MATERIALS AND METHODS: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. RESULTS: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. CONCLUSION: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships

Efficacy and safety of Intravitreal Aflibercept Vs Verteporfin Photodynamic Therapy in a Caucasian Population with Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial

Importance: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. Methods: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). Results: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] mu m in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] mu m [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. Conclusions and Relevance: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study

Gender variation in central serous chorioretinopathy

Background: Comparison of presentation and outcomes of central serous chorioretinopathy (CSC) between male and female subjects in different ethnic populations. Methods: Retrospective comparison between male and female subjects with CSC was completed. Demographic details, clinical presentations, imaging features and treatment outcomes were compared at baseline and at last follow-up. Results: This study included 155 male and 155 female subjects with a mean (CSD) age of 43.8 ± 10.3 and 57.0 ± 12.1 years, respectively, and a mean duration of follow-up of 8.49 ± 12.6 months. At presentation, there was no difference in visual acuity; however, visual acuity was significantly higher for female subjects at last follow-up (p = 0.02). Optical coherence tomography (OCT) analysis showed that subretinal deposits (p < 0.001), hyperreflective foci (p = 0.001), retinal pigment epithelial detachment (p = 0.01) and retinal pigment epithelium (RPE) irregularities (p = 0.03) were higher in male subjects at presentation. Angiographic analysis showed that diffuse leakage and RPE tracts were common in males (p = 0.01 and p = 0.02). No significant differences in choroidal dilatation or diffuse choroidal leakages were noted. Conclusions: Female subjects with CSC appear to have better outcomes, with less chances of diffuse RPE damage and other OCT features compared to males

New loci and coding variants confer risk for age-related macular degeneration in East Asians

加齢黄斑変性の発症に関わるアジア人特有の遺伝子変異を発見. 京都大学プレスリリース. 2015-02-05.Updated 30 March 2015. [Corrigendum] doi:10.1038/ncomms7817Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2, 119 patients with exudative AMD and 5, 691 controls, with independent replication in 4, 226 patients and 10, 289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10[-22]). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17mmoll-1 (P=5.82 × 10[-21]) in East Asians (n=7, 102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10[-18]), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10[-11]) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10[-8]). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature