Imaging in Neovascular Age-Related Macular Degeneration

Imaging plays an essential role in the diagnosis and treatment of age-related macular degeneration (AMD). This review describes the imaging modalities most commonly employed by ophthalmologists caring for patients with neovascular AMD. Imaging modalities discussed include fluorescein angiography, optical coherence tomography, indocyanine green angiography, and fundus autofluorescence.     

Verteporfin Therapy for Neovascular Age-Related Macular Degeneration in Indian Eyes

Purpose To determine visual outcome after a 12-month follow-up period of verteporfin therapy for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in Indian patients. Methods Twenty-five patients (26 eyes) who completed a 12-month follow-up after photodynamic therapy for subfoveal CNV secondary to AMD were included in the study. The follow-up schedule was every month for 2 months and then every 3 months thereafter until 12 months. Improvement in visual acuity was defined as a ≥10-letter gain, and deterioration as a ≥10-letter loss in the Early Treatment Diabetic Retinopathy Study chart at 4 m. Results The mean age of the 25 patients was 62.3 ± 9 years. There were 17 male patients (68%). The mean initial letter acuity was 28. 4 ± 14.1, and the final letter acuity was 25.5 ± 18.4 at 12 months. Initial visual acuity was ≥20/40 in seven eyes, 20/50–20/80 in nine eyes, and 20/100–20/200 in ten eyes; seven eyes had a ≥10-letter gain, and three eyes had a ≥10-letter loss. At the end of 12 months, six eyes had a ≥10-letter gain and ten eyes had a ≥10-letter loss. Conclusion Photodynamic therapy appears to preserve the vision in subfoveal CNV secondary to AMD in the eyes of Indian patients.     

Swept-Source OCT Angiographic Characteristics of Treatment-Naïve Nonexudative Macular Neovascularization in AMD Prior to Exudation

PurposeTo investigate the characteristics of treatment-naïve nonexudative macular neovascularization (MNV) in age-related macular degeneration before the onset of exudation using swept-source optical coherence tomography angiography.MethodsMNV area, choriocapillaris (CC) flow deficits (FDs), vessel area density (VAD), vessel skeleton density (VSD), retinal pigment epithelial detachment (PED) volume, mean choroidal thickness (MCT), and choroid vascularity index (CVI) measurements were assessed at two visits prior to exudation. We compared measurements made at the second visit and the rate of change between visits in eyes with and without exudation. The differences in these parameters between eyes with and without subsequent exudation were summarized with 95% confidence intervals (CIs).ResultsTwenty-one eyes with nonexudative MNV were identified and followed. Nine eyes developed exudation, and 12 eyes did not develop exudation. Differences between these groups of eyes for all parameters tended to be small, and the 95% CIs largely ruled out any substantial differences. Overall, eyes with exudation had 24% smaller VAD, 20% smaller VSD, and 33% smaller PED volume measurements. No noteworthy differences were observed for MNV area, CC FDs, MCT, or CVI measurements.ConclusionsThe onset of exudation was correlated with lesions having less vascularity and smaller PED volume measurements, but measurements of MNV area, CC FDs, MCT, and CVI were not correlated with near-term exudation. Investigations are ongoing to further explore these and other anatomic changes as harbingers of near-term exudation.     

Bevacizumab and Neovascular Age Related Macular Degeneration: Pathogenesis and Treatment

The pathogenesis of neovascular age related macular degeneration (AMD) is multifactorial including inflammation and angiogenesis leading to choroidal neovascularization (CNV). Therapy against vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular AMD. Intravitreal off-label use of bevacizumab proved to be safe. This literature review was conducted to study improvement in visual acuity, change in central retinal thickness (CRT), safety, pharmacodynamics, and possible resistance to intravitreal bevacizumab over a one-year period in eyes with neovascular AMD. We reviewed articles between 1997 and January 2010 that included at least 30 patients with AMD who received intravitreal bevacizumab monotherapy for at least 1 year. The mean number of letters gained, decrease in CRT, and number of injections were 8 letters, 125.3?µm, and 4.3 injections, respectively. Further, randomized prospective clinical trials are needed to determine the efficacy and safety of intravitreal bevacizumab in the treatment of neovascular AMD.     

Self-Reported Sleep Duration in Patients with Neovascular Age-Related Macular Degeneration

Purpose: To examine the relationship between self-reported sleep duration and neovascular age-related macular degeneration (nAMD).

Methods: This case-control study comprised 165 subjects (57 patients with nAMD and 108 controls). Controls were matched to cases by age and sex. Participants completed a questionnaire that included questions about sleep duration and quality. Four categories of sleep duration were established; <6 hours, 6–7 hours, 7–8 hours and >8 hours. Association of sleep duration and nAMD was assessed by logistic regression analysis. Multiple logistic regression models were performed to control for possible confounders.

Results: We found a significant association between short sleep duration and nAMD (for <6 hours, odds ratio, OR, 3.29, 95% confidence interval, CI, 1.32–8.27; for 6–7 hours, OR 2.25, 95% CI 0.80–6.32; and for >8 hours, OR 1.39, 95% CI 0.53–3.73) compared with the reference category of 7–8 hours. This association remained significant after adjustment for confounders (<6 hours, OR 3.09, 95% CI 1.20–7.97). In addition, a borderline significant association was observed between self-reported very bad sleep quality and nAMD (OR 2.84, 95% CI 1.02–7.88). The highest rate of sleep medication use was found in the nAMD group (p < 0.001).

Conclusion: Our findings provide evidence to support an association between short sleep duration and nAMD. Considering strategies to improve sleep in these patients may prevent the negative effects of sleep deficiency.     

Choriocapillaris Flow Imbalance in Fellow Eyes in Age-Related Macular Degeneration

PurposeThe purpose of this study was to identify early changes in choriocapillaris flow in patients with age-related macular degeneration (AMD) with no history of macular neovascularization (MNV).MethodsClinical records of fellow eyes of patients with unilateral neovascular AMD without fundus findings and control eyes of otherwise healthy individuals, except for mild cataract, diagnosed at St. Luke''s International Hospital from April 2020 to March 2021, were retrospectively analyzed. Optical coherence tomography (OCT) angiography images of the choriocapillaris slab were binarized using the Phansalkar local thresholding methods to evaluate the choriocapillaris flow area (CCFA) and its coefficient of variation (CV).ResultsThe data of 24 AMD fellow eyes (17 for men, 71.7 ± 1.9 years old) and 21 control eyes (11 for men, 69.1 ± 2.0 years old) were analyzed. The mean CCFA ratio was lower in the AMD fellow eyes (58.6 ± 1.2%) than in the control eyes (62.4 ± 1.3%, P = 0.032), and the mean CV of CCFA ratio was greater in the AMD fellow eyes (0.174 ± 0.007) than in the control eyes (0.154 ± 0.007, P = 0.032). Eyes with CCFA ratio <60% and CV of CCFA ratio ≥0.154 had a 4.371-fold higher risk of being AMD fellow eyes (95% confidence interval = 1.029–18.56, P = 0.046). Differences in CV of CCFA ratio between AMD fellow eyes and control eyes were particularly clear in eyes with thick choroids (mean CV of CCFA in control versus AMD fellow eyes with central choroidal thickness ≥220 µm: 0.144 ± 0.005 vs. 0.173 ± 0.007, P = 0.009**).ConclusionsNeovascular AMD fellow eyes without MNV had reduced, heterogeneous, and imbalanced choriocapillaris flow, which may constitute early changes in neovascular AMD, although further studies are required.     

Surgical Excision of Type 2 Choroidal Neovascularization in Age-Related Macular Degeneration

Purpose To evaluate the visual acuity outcome and the influence of various factors on visual outcome in patients undergoing surgical removal of type 2 choroidal neovascular neovascularization (CNV) caused by age-related macular degeneration (AMD).Methods We studied the records of 92 patients (92 eyes) who were followed for at least 1 year after surgical excision of CNV associated with AMD.Results The final visual acuity was 0.4 or better in 21%, 0.1 to 0.3 in 66%, and worse than 0.1 in 13% of the patients. Final visual acuity was improved in 62%, stable in 29%, and worse in 9%. Stepwise regression identified CNV size as a significant factor influencing final visual acuity (R = 0.287, P = 0.0045).Conclusions Surgical excision of CNV for AMD is indicated for patients with subfoveal active type 2 CNV with a visual acuity of 0.3 or worse. To achieve better postoperative visual acuity it is important to operate on AMD patients in the early stage of CNV. Jpn J Ophthalmol 2005;49:321–323 © Japanese Ophthalmological Society 2005     

基于电子化信息平台的新生血管性年龄相关性黄斑变性真实世界研究进展

年龄相关性黄斑变性（AMD）是目前全球致盲的主要病因之一。抗血管内皮生长因子（Anti-VEGF）疗法已成为新生血管性AMD的一线治疗方案。考虑到抗VEGF药物的费用昂贵，患者需要长期甚至终身接受反复抗VEGF注射治疗，了解真实世界中抗VEGF的治疗情况，对于指导临床实践、改善患者诊疗路径乃至卫生决策都十分重要。近年来基于电子化信息平台的新生血管性AMD数据分析研究向我们展现了不同国家和地区新生血管性AMD的流行病学、真实世界抗VEGF的治疗情况以及医疗支出等，笔者就此作一综述。     

Complement Activation Products and Cytokines in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration

PurposeTo investigate the characteristics of complement activation products and angiogenic cytokines in the aqueous humor in eyes with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD).MethodsThis was a prospective, comparative, observational study. All patients with choroidal neovascularization were classified as PNV without polyps, PNV with polyps (polypoidal choroidal vasculopathy [PCV]), or drusen-associated nAMD according to the presence or absence of pachychoroid features and soft drusen. This study included a total of 105 eyes. Aqueous humor samples were collected from 25 eyes with PNV without polyps, 23 eyes with PCV, and 24 eyes with drusen-associated nAMD before intravitreal anti-vascular endothelial growth factor (VEGF) injection and cataract surgery in 33 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, C5a, VEGF, and macrophage chemoattractant protein 1 (MCP-1) using a bead-based immunoassay.ResultsC3a and MCP-1 levels were significantly higher in PCV (P = 0.032 and P = 0.039, respectively) and drusen-associated nAMD (P = 0.01 for both comparisons) than in controls, and no difference was seen in C3a and MCP-1 levels between PNV and controls (P = 0.747 and P = 0.294, respectively). VEGF levels were significantly higher in PNV (P = 0.016), PCV (P = 0.009), and drusen-associated nAMD (P = 0.043) than in controls. In PNV, the VEGF levels elevated without elevated C3a and MCP-1.ConclusionsPNV, PCV, and drusen-associated nAMD had significantly distinct profiles of complement activation products and cytokines in the aqueous humor.     

Scotopic Sensitivity of Central Retina in Early Age-Related Macular Degeneration

Purpose: To test scotopic sensitivity and investigate whether there is rod system dysfunction in the central retina in early age - related macular degeneration (AMD). Methods: Scotopic(450 nm stimulus) and photopic (white light stimulus) sensitivity in 24 patients with early AMD was measured at 81 loci in central 25° of retina, and compared with the age - match normal controls.Results: Mean scotopic sensitivity of AMD patients was significantly lower than that of the normal controls. The patients of reduced scotopic sensitivity were more than those of reduced photopic sensitivity. Scotopic sensitivity deficit decreased with increasing eccentricity with the greatest deficit was 2. 5° to 5. 0°.Conclusions: Scotopic sensitivity was decreased in the early stage of AMD. The parafoveal rod cells were selectively damaged in AMD. Scotopic sensitivity testing in macula may be a useful tool to diagnose and measure the fundus dysfunction of AMD. Eye Science 2003; 19: 15 - 19.     

Surgical Excision of Type 1 + 2 Choroidal Neovascularization in Age-Related Macular Degeneration

Purpose To evaluate the visual acuity outcome and the various factors influencing visual outcome in patients undergoing surgical removal of type 1 + 2 choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD).Methods We studied the records of 54 patients (54 eyes) followed for at least 1 year after surgical excision of CNV associated with AMD.Results The final visual acuity was 0.4 or better in 4%, 0.1 to 0.3 in 46%, and worse than 0.1 in 50% of the patients. Final visual acuity was improved in 39%, stable in 37%, and worse in 24%. Stepwise regression showed that the distance between the center of the foveal avascular zone and the CNV margin had the greatest effect on final visual acuity.Conclusions Surgical excision of type1 + 2 CNV due to AMD may be indicated for preserving preoperative visual acuity. The distance between the center of the foveal avascular zone and the CNV margin is the most important factor affecting final visual acuity. Jpn J Ophthalmol 2005;49:324–326© Japanese Ophthalmological Society 2005     

Effects of Vitreomacular Traction on Ranibizumab Treatment Response in Eyes with Neovascular Age-related Macular Degeneration

PurposeTo investigate the effects of vitreomacular traction (VMT) on ranibizumab treatment response for neovascular age-related macular degeneration (AMD).MethodsA retrospective review of 85 eyes of 85 patients newly diagnosed with neovascular AMD was conducted. Patients were eligible if they had received more than three consecutive monthly ranibizumab (0.50 mg) treatments and ophthalmic evaluations. Patients were classified into a VMT (+) group or VMT (-) group according to optical coherence tomography imaging. Best corrected visual acuity and central retinal thickness (CRT) measurements were obtained at three and six months after initial injection.ResultsOne month after the third injection, mean visual acuity (VA) increases of 6.36 and 9.87 letters were observed in the VMT (+) and VMT (-) groups, respectively. The corresponding mean CRT values decreased by 70.29 µm and 121.68 µm, respectively. A total 41 eyes were identified as eligible for a subsequent fourth injection; 71.1% of patients (27 eyes) in the VMT (+) group but only 29.8% of patients in the VMT (-) group needed a subsequent fourth injection. Follow-up was extended to six months for 42 of the 85 enrolled patients (49.4%). The trends in VA and optical coherence tomography were found to be maintained at six-month follow-up.ConclusionsVA and CRT appeared to be more improved after ranibizumab treatment in the VMT (-) group compared to the VMT (+) group. VMT might antagonize the effect of ranibizumab treatment in a subpopulation of AMD patients.     

Characteristics of Indocyanine Green Angiography in Exudative Age—related Macular Degeneration

Objective: To observe the characteristics of indocyanine green angiography (ICGA) in exudative age-related macular degeneration (AMD).Methods: Thirty-one cases (39 eyes) were diagnosed as exudative AMD by ocular examination, fundus color photography, fundus fluorescein angiography (FFA) and ICGA. Their ages ranged from 50 to 82 years and visual acuities from FC/30cm to 0. 7. We analyzed and compared the characteristics of ICGA and FFA in these patients. Results: Of 26 eyes with occult choroidal neovascularization (CNV) by FFA, 15 (57. 7% ) had classic CNV by ICGA. Of 4 eyes with serous retinal pigment epithelial detachment (FED) without CNV by FFA, 1 had serous FED with classic CNV by ICGA. The hyperfluorescence of the scar staining was detecfed by ICGA. Conclusion ? ICGA adds clinically useful information and is an important adjunct in the evaluation, classification, and laser treatment of patients with occult CNV in AMD. Eye Science 1999; 15: 156 - 161.     

Radial Peripapillary Capillary Plexus Sparing and Underlying Retinal Vascular Impairment in Intermediate Age-Related Macular Degeneration

PurposeTo examine location-specific retinal vascular changes in intermediate age-related macular degeneration (iAMD) using age-matched, high-density en face optical coherence tomography angiography (OCTA) cluster analysis.MethodsEn face OCTA images of the 6 × 6 mm macular area were retrospectively acquired from 60 iAMD eyes and 60 age-matched normal eyes and then subdivided into 126 × 126 (47.62 × 47.62 µm) grids within the superficial and deep vascular complex. Grid-wise vessel perfusion (VP) were compared between iAMD and normal eyes from the corresponding 10-yearly age cohort, forming difference plots. Difference plots were further separated by normative topographical map spatial clusters (C_1-6), derived from normal_database eyes (n = 236, 20–81 years old).ResultsOverall difference plots showed decreased VP in the superficial (−12.19%) and deep vascular complex (−6.44%) of iAMD compared to normal eyes (P < 0.0001 both comparisons). Cluster-based difference plots highlighted nonuniform changes in the superficial vascular complex, with sparing of VP at the nasal macula (corresponding to the radial peripapillary capillary plexus) versus decreased VP toward the temporal macula and foveal avascular zone (FAZ) (C_1–6 all comparisons P < 0.0001, except C₁ vs. C₂ P > 0.99 and C₄ vs. C₅ P = 0.11). The deep vascular complex displayed diffusely decreased VP, greater at the FAZ (P < 0.0001).ConclusionsHigh-density en face OCTA cluster analysis suggests relative sparing of the radial peripapillary capillary plexus and impairment of underlying retinal vasculature, supporting potential anterograde transsynaptic degeneration in iAMD. These location-specific data may better guide future diagnostic and management protocol of iAMD.     

Fundus Autofluorescence Imaging in Age-Related Macular Degeneration

Abstract

Fundus autofluorescence (FAF) is a noninvasive imaging technology that provides information on the distribution of lipofuscin within the retinal pigment epithelial cells. Progressive accumulation of lipofuscin within retinal pigment epithelial cells is involved in the pathogenesis of age-related macular degeneration (AMD). Fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope is a useful technique to identify high-risk characteristics in patients with nonexudative AMD. It gives also some valuable knowledge and clues in differantial diagnosis of exudative age-related macular degeneration. This review comprises an introduction to fundus autofluorescence, a review of FAF imaging in AMD, and the recent classification of geographic atrophy (GA) and early AMD phenotypes by the Fundus Autofluorescence in Age-related Macular Degeneration Study. The association of phenotype and atrophy progression and choroidal neovascularization development are also summarized.