Smoking Is a Risk Factor for Pahcychoroid-related Disorders in Asian Patients: a Case Control Study

BackgroundCigarette smoking has been reported as a risk factor for the development of neovascular age-related macular degeneration (nAMD). However, the associations between cigarette smoking and subtypes of drusen and nAMD were incomplete, as it lacked consideration of pachydrusen or no significant drusen. Therefore, this study intended to reveal the associations between cigarette smoking and subtypes of drusen and nAMD.PurposeTo evaluate the associations between cigarette smoking and subtypes of drusen and nAMD in an Asian population.MethodsThis retrospective case-control study included 189 eyes in 189 patients with treatment-naïve nAMD, including typical AMD, polypoidal choroidal vasculopathy (PCV), and type 3 neovascularization. The patients were stratified into never-, former-, and current-smoker groups, and drusen subtypes, including no significant drusen, soft drusen, subretinal drusenoid deposits (SDDs), and pachydrusen, were analyzed in each group.ResultsThe proportions of no significant drusen and pachydrusen in the fellow eyes were significantly higher in the former- and current-smoker groups (P = 0.016 and P < 0.001), respectively. There was a significantly higher proportion of PCV in the affected eyes in the current-smoker group (P = 0.041). The proportions of SDDs in the fellow eyes and type 3 neovascularization in the affected eyes were significantly higher in the never-smoker group (P < 0.001 and P = 0.037), respectively.ConclusionEver smokers (former and current smokers) had significantly higher proportions of pachychoroid-related disorders, including no significant drusen, pachydrusen, and PCV, than nonsmokers. Thus, cigarette smoking could be a risk factor for the development of pachychoroid-dependent abnormalities.

Unaffected fellow eye neovascularization in patients with type 3 neovascularization: Incidence and risk factors

Purpose To evaluate the incidence and risk factors of neovascularization in unaffected fellow eyes of patients diagnosed with type 3 neovascularization in Korea. Methods This retrospective study included 93 unaffected fellow eyes of 93 patients diagnosed with type 3 neovascularization. For initial type 3 neovascularization diagnosis, optical coherence tomography and angiography were conducted. These baseline data were compared between patients with and without neovascularization in their fellow eyes during the follow-up period. Results The mean follow-up period was 66.1±31.1 months. Neovascularization developed in 49 (52.8%) fellow eyes after a mean period of 29.5±19.6 months. In the fellow eye neovascularization group, the incidence of soft drusen and reticular pseudodrusen was significantly higher than that in the non-neovascularization group (83.7% vs. 36.5%, p<0.001; 67.3% vs. 40.9%, p = 0.017, respectively), but the choroidal vascularity index (CVI) showed a significantly lower value (60.7±2.0% vs. 61.7±2.5%; p = 0.047). The presence of reticular pseudodrusen was related with the duration from baseline to development of fellow eye neovascularization (p = 0.038). Conclusion Neovascularization developed in 52.8% of unaffected fellow eyes. The presence of soft drusen, reticular pseudodrusen, and lower CVI values can be considered risk factors of neovascularization in unaffected fellow eyes of patients with type 3 neovascularization. The lower CVI values suggest that choroidal ischemic change may affect the development of choroidal neovascularization in these patients.

Eyes that Do Not Meet the Eligibility Criteria of Clinical Trials on Age-Related Macular Degeneration: Proportion of the Real-World Patient Population and Reasons for Exclusion

Background. To evaluate the proportion of eyes that do not meet the eligibility criteria of clinical trials on neovascular age-related macular degeneration (AMD) and the reasons for exclusion. Methods. This retrospective, observational study included 512 eyes of 463 patients diagnosed with treatment-naïve neovascular AMD. The proportion of eyes that did not meet the eligibility criteria of the Vascular Endothelial Growth Factor Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies were evaluated. The two most common reasons for exclusion were also evaluated in each subtype of neovascular AMD (typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), and type 3 neovascularization). Results. Among the 512 eyes, 229 (44.7%) did not meet the eligibility criteria. In all the included eyes, the most common reasons for exclusion were good or poor visual acuity (169 eyes, 33.0%), followed by the presence of subretinal hemorrhage (47 eyes, 9.5%). Moreover, good or poor visual acuity was the most common reason for exclusion in all three subtypes of neovascular AMD. The second most common reason was a fovea-involving scar or fibrosis in typical neovascular AMD, subretinal hemorrhage in PCV, and other vascular diseases affecting the retina in type 3 neovascularization. Conclusions. Among the included cases, 44.7% did not meet the eligibility criteria for VIEW study, suggesting that the conclusion derived from clinical trials may not directly reflect the real-world outcomes. Additionally, the reasons for ineligibility differed among the different subtypes of neovascular AMD.

An Evaluation of the Microvasculature of Macular Nodules in Coats Disease Using Optical Coherence Tomography Angiography: A Report of 3 Cases

Purpose: This work aimed to examine the microvasculature of macular fibrosis in Coats disease. Methods: Three boys (aged 3, 4, and 6 years) with Coats disease (stages 2B to 3A2) and macular fibrotic nodules were imaged using optical coherence tomography angiography (OCTA) on the Spectralis spectral-domain OCT tabletop and investigational portable Spectralis Flex module (version 6.9, Heidelberg Engineering). Results: In 2 eyes, a neovascular complex was observed in the avascular slab on OCTA. This neovascular complex had vessels connected to diving vessels from the superficial vascular complex that traveled through the deep vascular complex to the avascular complex. In the third eye, no neovascular complex was observed on OCTA at presentation, but on subsequent examinations fluorescein leakage was observed and cross-sectional OCTA further confirmed the presence of angiographic flow in the nodule. Conclusions: OCTA demonstrates the presence of type 3 neovascularization in fibrotic nodules in Coats disease.

Multimodal imaging to detect in vivo responses to aflibercept therapy in a mouse model of type 3 neovascularization

Purpose: To characterize the response to aflibercept in a mouse model of type 3 neovascularization, the neoretinal vascularization (NRV) 2 mouse line. Methods: Twelve NRV2 mice were assigned to one of the following groups: (i) six mice were injected with aflibercept 3µg/g at postnatal day 15 (“aflibercept” group), and (ii) the remaining six mice did not receive any treatment (“placebo” group). Mice were examined at postnatal day 30 (p30) and 44 (p44). Results: The NRV mice’s retinas were characterized by regions of depigmentation that were topographically associated with hyperfluorescent lesions seen on fluorescein angiography (FA) images. On optical coherence tomography (OCT) images, intraretinal neovascularizations were visualized as hyperreflective lesions mainly localized within the outer plexiform and outer nuclear layers. The average number of intraretinal neovascular lesions visualized on FA at P30 was 5.0±2.2 in the “aflibercept” and 20.7±2.4 in the “placebo” groups (p<0.0001). At P44, the average number of intraretinal lesions was still lower in the “aflibercept” group, although this difference was not statistically significant (p=0.088). Conclusion: Aflibercept therapy was effective in inhibiting the pathologic angiogenesis in the NRV2 mouse model. However, the successive treatment washout resulted in an increase in lesions’ number.

Optical Coherence Tomography Findings (SD-OCT and OCTA) in Early-Stage Type 3 Neovascularization

A 76-year-old male presented with a small hyperreflective density in the outer nuclear layer with subtle retinal pigment epithelium (RPE) elevation and few intraretinal cysts on spectral-domain optical coherence tomography (SD-OCT). Optical coherence tomography angiography (OCTA) confirmed the presence of a tuft-shaped intraretinal neovascular lesion. SD-OCT performed 2 months before showed a smaller RPE elevation at the same location without intraretinal fluid. A 79-year-old male presented with a small hyperreflective density in the outer retina surrounded by scant intraretinal fluid on SD-OCT and a bright vessel on OCTA, suggesting early-stage type 3 neovascularization. SD-OCT performed 2 months before showed a smaller hyperreflectivity at the same location, without intraretinal fluid. An 84-year-old female presented with hyperreflective foci in the outer retina overlying a serous pigment epithelium detachment (PED) with focal RPE disruption on SD-OCT. SD-OCT performed 2 months before showed the same hyperreflective lesion associated with a shallower PED. No neovascular lesions were found on OCTA after six injections of bevacizumab. To conclude, careful evaluation of SD-OCT allows for early detection of type 3 neovascularization at a pre-exudative stage. OCTA may be useful in confirming the presence of intraretinal neovascular lesion and monitoring response to anti-vascular endothelial growth factor agents.