DEVELOPMENT AND VALIDATION OF AN EXPLAINABLE ARTIFICIAL INTELLIGENCE FRAMEWORK FOR MACULAR DISEASE DIAGNOSIS BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES.

PURPOSE: To develop and validate an artificial intelligence framework for identifying multiple retinal lesions at image level and performing an explainable macular disease diagnosis at eye level in optical coherence tomography images. METHODS: A total of 26,815 optical coherence tomography images were collected from 865 eyes, and 9 retinal lesions and 3 macular diseases were labeled by ophthalmologists, including diabetic macular edema and dry/wet age-related macular degeneration. We applied deep learning to classify retinal lesions at image level and random forests to achieve an explainable disease diagnosis at eye level. The performance of the integrated two-stage framework was evaluated and compared with human experts. RESULTS: On testing data set of 2,480 optical coherence tomography images from 80 eyes, the deep learning model achieved an average area under curve of 0.978 (95% confidence interval, 0.971-0.983) for lesion classification. In addition, random forests performed accurate disease diagnosis with a 0% error rate, which achieved the same accuracy as one of the human experts and was better than the other three experts. It also revealed that the detection of specific lesions in the center of macular region had more contribution to macular disease diagnosis. CONCLUSION: The integrated method achieved high accuracy and interpretability in retinal lesion classification and macular disease diagnosis in optical coherence tomography images and could have the potential to facilitate the clinical diagnosis.

OCT-A characterisation of recurrent type 3 macular neovascularisation.

PURPOSE: To investigate optical coherence tomography angiography (OCT-A) findings in recurrent type 3 macular neovascularisation (MNV). METHODS: In this retrospective cohort study, consecutive patients with type 3 MNV secondary to age-related macular degeneration underwent OCT-A at three different time points: baseline, after anti-vascular endothelial growth factor treatment with complete resolution of the exudative signs (ie, non-exudative stage) and at the recurrence of exudation (ie, recurrence stage). Demographics and clinical findings were analysed, including OCT-A features of type 3 MNV recurrence. RESULTS: Twelve eyes (12 patients, mean age 78±7 years) were included. Using OCT-A, at baseline all type 3 MNVs showed the presence of detectable flow downgrowing from the deep vascular complex (DVC) to the retinal pigment epithelium (RPE)/sub-RPE space. 6/12 eyes (50%) showed anomalous flow under the RPE, while the other 6 eyes showed flow reaching the RPE without anomalous flow in the sub-RPE space. At the non-exudative stage (after treatment), BCVA and CMT significantly improved (p=0.004 and p=0.036), and flow inside the retinal lesions reduced; interestingly the connection to the RPE/sub-RPE space regressed. At the time of recurrence, all type 3 MNVs showed the presence of intra/sub-retinal exudation with restoration of the flow deepening from the DVC to the RPE/sub-RPE space. CONCLUSIONS: Detectable flow deepening from the DVC to the RPE/sub-RPE space using OCT-A is mandatory to have a new exudation secondary to recurrent type 3 MNV. Early detection of type 3 MNV recurrence by OCT-A characterisation may prompt retreatment and potentially prevent progression to late stages of the disease.

VISUAL PROGNOSIS AFTER PNEUMATIC DISPLACEMENT OF SUBMACULAR HEMORRHAGE ACCORDING TO AGE-RELATED MACULAR DEGENERATION SUBTYPES.

PURPOSE: This study compared the visual outcome after pneumatic displacement of submacular hemorrhage among patients with different subtypes of age-related macular degeneration (AMD). METHODS: We retrospectively reviewed the medical records of 67 patients (67 eyes) who underwent treatment for submacular hemorrhage associated with AMD. All the patients underwent pneumatic displacement. Demographic parameters, visual acuity, and anatomical features were analyzed among AMD subtypes: typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). RESULTS: Among the eyes with submacular hemorrhage, 24, 30, and 13 eyes had typical AMD, PCV, and RAP, respectively. Post-treatment best-corrected visual acuity was best in the PCV group and worst in the RAP group (P < 0.001). The proportion of eyes with improved visual acuity was highest in the PCV subtype and lowest in the RAP subtype (P = 0.044). Logistic regression analysis showed that AMD subtype (P = 0.016) and time to treatment (<7 days) (P = 0.037) are associated with the final visual outcome. CONCLUSION: The final post-treatment visual outcome after the incidence of submacular hemorrhage was best in the PCV group and worst in the RAP group. Age-related macular degeneration subtype is a significant factor associated with the visual prognosis of submacular hemorrhage.

Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.

PURPOSE: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN: Consensus meeting. PARTICIPANTS: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES: A consensus classification of neovascular AMD. RESULTS: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

COLORADO AGE-RELATED MACULAR DEGENERATION REGISTRY: Design and Clinical Risk Factors of the Cohort.

PURPOSE: To study new and existing risk factors related to age-related macular degeneration (AMD) phenotypes in a Colorado cohort. METHODS: Age-related macular degeneration was categorized into early, intermediate, or advanced forms. Controls (n = 180) were patients with cataract and no AMD. Demographic and clinical data were gathered by patient interview and verified by chart review. Image data were reviewed by vitreoretinal specialists. Statistical analysis included univariable and multivariate logistic regression analysis (P < 0.05). RESULTS: Among the 456 patients with AMD, 157 (34.4%), 80 (17.6%), and 219 (48.0%) had the early/intermediate, geographic atrophy, and neovascular forms of the disease, respectively. Adjusted for age, African-American race was associated with a reduced risk of early/intermediate (adjusted odds ratio [AOR] = 0.08, confidence interval [CI] = 0.01-0.67) and neovascular AMD (AOR = 0.15, CI = 0.03-0.72). A family history of AMD was a risk factor for early/intermediate (AOR = 4.08, CI = 2.30-7.25), geographic atrophy (AOR = 8.62, CI = 3.77-19.7), and neovascular AMD (AOR = 3.76, CI = 2.16-6.56). A history of asthma was related to the early/intermediate form of AMD (AOR = 2.34, CI = 1.22-4.46). CONCLUSION: Studying AMD in specific populations may reveal novel risk factors such as our finding of a relationship between asthma history and AMD.

Variable response of subretinal hyperreflective material to anti-vascular endothelial growth factor classified with optical coherence tomography angiography.

PURPOSE: To evaluate the prognosis and response of neovascular age-related macular degeneration (AMD) to anti-vascular endothelial growth factor (VEGF), according to the components of subretinal hyperreflective material (SHRM) classified using optical coherence tomography angiography (OCTA), is the aim of this study. METHODS: We retrospectively studied 39 eyes of 39 consecutive patients with SHRM associated with exudative AMD, who underwent standard examination and multimodal imaging, including fundus photography, optical coherence tomography (OCT), and OCTA. We classified SHRM into type 2 neovascularization (NV), fibrosis, subretinal hyperreflective exudation (SHE), and hemorrhage using OCTA. If compound SHRM was found, components in the foveal center were considered. All patients except one with fibrosis received anti-VEGF treatment for more than 12 months. The best-corrected visual acuity (BCVA) values measured before treatment and at 3, 6, and 12 months after the first injection were compared according to the components of SHRM. RESULTS: Using OCTA, 11 eyes with type 2 NV showed abnormal blood flow and 1 eye with fibrosis showed strong surface projection. Both SHE and hemorrhage components showed projection artifact with no intrinsic flow. However, OCTA enabled eyes with SHE (17 eyes) to be distinguished from those with hemorrhage (10 eyes) because hemorrhage showed masking of choriocapillaris flow. Eyes with SHE showed a significant improvement in the mean logMAR BCVA as compared with the value at the baseline, which was sustained throughout the 12-month follow-up period (p < 0.05). In eyes with type 2 NV and hemorrhage, no significant difference in the mean BCVA values was observed at any follow-up time-point (all, p > 0.05). CONCLUSION: OCTA was useful to noninvasively distinguish SHRM components. It may be important to consider the components of SHRM to predict the visual acuity in patients with AMD.

Prevalence of Age-Related Macular Degeneration in Australia: The Australian National Eye Health Survey.

Importance: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among the elderly population globally. Currently, knowledge of the epidemiology of AMD in Australia remains scarce because of a paucity of recent population-based data. Objective: To examine the prevalence of AMD in Australia. Design, Setting, and Participants: In this population-based, cross-sectional survey performed from March 11, 2015, to April 18, 2016, a sample of 3098 nonindigenous Australians 50 years and older and 1738 indigenous Australians 40 years and older from 30 geographic areas across Australia were examined. Main Outcomes and Measures: Any AMD, early AMD, intermediate AMD, and late AMD graded according to the Beckman clinical classification system. Results: A total of 4836 individuals were examined, including 3098 nonindigenous Australian (64.1%; 58.9% female vs 41.1% male; age range, 40-92 years; mean [SD] age, 55.0 [10.0] years) and 1738 indigenous Australians (35.9%; 53.6% female vs 46.4% male; age range, 50-98 years; mean [SD] age, 66.6 [9.7] years). A total of 4589 (94.9%, 2946 nonindigenous and 1643 indigenous) participants had retinal photographs in at least 1 eye that were gradable for AMD. The weighted prevalence of early AMD was 14.8% (95% CI, 11.7%-18.6%) and of intermediate AMD was 10.5% (95% CI, 8.3%-13.1%) among nonindigenous Australians. In indigenous Australians, the weighted prevalence of early AMD was 13.8% (95% CI, 9.7%-19.3%) and of intermediate AMD was 5.7% (96% CI, 4.7%-7.0%). Late AMD was found in 0.96% (95% CI, 0.59%-1.55%) of nonindigenous participants (atrophic, 0.72%; neovascular, 0.24%). The prevalence of late AMD increased to 6.7% in participants 80 years or older and was higher in men (1.4% vs 0.61%, P = .02). Only 3 (0.17% [95% CI, 0.04%-0.63%]) indigenous participants had late (atrophic) AMD. Age-related macular degeneration was attributed as the main cause of vision loss (<6/12 in the better eye) in 23 of 208 nonindigenous Australians (11.1%) and 2 of 183 indigenous Australians (1.1%). Conclusions and Relevance: In line with data from other white populations, AMD is a prominent cause of vision loss in the nonindigenous Australian population. An increased provision of low vision rehabilitation services may be required to cope with the projected increase in AMD in Australia.

Postreceptor Neuronal Loss in Intermediate Age-related Macular Degeneration.

PURPOSE: To investigate the relationship between ganglion cell complex (GCC) thickness and photoreceptor alterations in eyes with intermediate age-related macular degeneration (AMD). DESIGN: Retrospective case-control study. METHODS: We collected data from 68 eyes with intermediate AMD from 68 patients with spectral-domain optical coherence tomography (SDOCT) imaging. A control group of 50 eyes from 50 healthy subjects was included for comparison. Our main outcome measures for comparison between groups were (1) the average and minimum GCC thickness and (2) the "normalized" reflectivity of the ellipsoid zone (EZ) en face image. RESULTS: The average and minimum GCC thicknesses were thinner in AMD patients (69.54 ± 9.30 µm and 63.22 ± 14.11 µm, respectively) than in healthy controls (78.57 ± 6.28 µm and 76.28 ± 6.85 µm, P < .0001 and P < .0001, respectively). Agreement was found to be excellent in the "normalized" EZ reflectivity assessment (intraclass correlation coefficient = 0.986, coefficient of variation = 1.11). The EZ "normalized" reflectivity was 0.67 ± 0.11 in controls and 0.61 ± 0.09 in the AMD group (P = .006). In univariate analysis, EZ "normalized" reflectivity was found to have a significant direct relationship with average (P < .0001) and minimum (P < .0001) GCC thickness in AMD patients, but not in controls (P = .852 and P = .892, respectively). CONCLUSIONS: Eyes with intermediate AMD exhibit GCC thinning, as well as a reduced EZ "normalized" reflectivity, and these parameters are correlated. This study supports the concept of postreceptor retinal neuronal loss as a contributor to retinal thinning in intermediate AMD.

Classification of Exudative Age-Related Macular Degeneration With Pachyvessels on En Face Swept-Source Optical Coherence Tomography.

Purpose: The purpose of this study was to classify exudative maculopathy by the presence of pachyvessels on en face swept-source optical coherence tomography (SSOCT). Methods: Consecutive patients with signs of exudative maculopathy underwent SSOCT, fluorescein and indocyanine green angiography (ICGA), ultra-widefield fundus color photography, and autofluorescence examinations. Images were analyzed in a masked fashion by two sets of four examiners in different sessions: (1) the presence of pachyvessels in en face OCT and (2) features of exudative maculopathy in conventional imaging modalities. Quantitative data obtained were subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI), which was the ratio of choroidal vessels lumen area to a specified choroidal area from binarized cross-sectional OCT scans. Results: Pachyvessels was observed in 38 (52.1%) of 73 eyes. The pachyvessels group was associated with younger age (69.1 ± 9.4 years, odds ratio [OR] = 0.95, 95% confidence interval [95% CI] = 0.90-0.97, P = 0.04), presence of polypoidal lesions (OR = 3.27, 95% CI = 1.24-8.62, P = 0.01), increased SFCT (OR = 1.08, 95% CI = 1.02-1.14, P < 0.01), and increased CVI (65.4 ± 5.3, OR = 1.12, 95% CI = 1.02-1.23, P = 0.01). In multivariate regression, CVI significantly correlated with pachyvessels (OR = 1.24, 95% CI = 1.03-1.55, P = 0.04). Conclusions: Exudative maculopathy could be classified based on differences in choroidal vasculature morphology. Current results implied that choroidal hemodynamics may be relevant to variable natural history and treatment response in neovascular AMD and polypoidal choroidal vasculopathy.

Imaging Protocols in Clinical Studies in Advanced Age-Related Macular Degeneration: Recommendations from Classification of Atrophy Consensus Meetings.

PURPOSE: To summarize the results of 2 consensus meetings (Classification of Atrophy Meeting [CAM]) on conventional and advanced imaging modalities used to detect and quantify atrophy due to late-stage non-neovascular and neovascular age-related macular degeneration (AMD) and to provide recommendations on the use of these modalities in natural history studies and interventional clinical trials. DESIGN: Systematic debate on the relevance of distinct imaging modalities held in 2 consensus meetings. PARTICIPANTS: A panel of retina specialists. METHODS: During the CAM, a consortium of international experts evaluated the advantages and disadvantages of various imaging modalities on the basis of the collective analysis of a large series of clinical cases. A systematic discussion on the role of each modality in future studies in non-neovascular and neovascular AMD was held. MAIN OUTCOME MEASURES: Advantages and disadvantages of current retinal imaging technologies and recommendations for their use in advanced AMD trials. RESULTS: Imaging protocols to detect, quantify, and monitor progression of atrophy should include color fundus photography (CFP), confocal fundus autofluorescence (FAF), confocal near-infrared reflectance (NIR), and high-resolution optical coherence tomography volume scans. These images should be acquired at regular intervals throughout the study. In studies of non-neovascular AMD (without evident signs of active or regressed neovascularization [NV] at baseline), CFP may be sufficient at baseline and end-of-study visit. Fluorescein angiography (FA) may become necessary to evaluate for NV at any visit during the study. Indocyanine-green angiography (ICG-A) may be considered at baseline under certain conditions. For studies in patients with neovascular AMD, increased need for visualization of the vasculature must be taken into account. Accordingly, these studies should include FA (recommended at baseline and selected follow-up visits) and ICG-A under certain conditions. CONCLUSIONS: A multimodal imaging approach is recommended in clinical studies for the optimal detection and measurement of atrophy and its associated features. Specific validation studies will be necessary to determine the best combination of imaging modalities, and these recommendations will need to be updated as new imaging technologies become available in the future.

PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

PURPOSE: To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. METHODS: Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. RESULTS: Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001). CONCLUSION: Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

Optical Coherence Tomography Angiography of Type 2 Neovascularization in Age-Related Macular Degeneration.

Well-defined choroidal neovascularization, known as type 2 neovascularization (NV) or classic NV, is the least representative phenotype of exudative age-related macular degeneration. Clinical aspects of type 2 NV have been widely described in the literature, and to date fluorescein angiography remains the gold standard for imaging age-related macular degeneration at initial presentation. Optical coherence tomography angiography (OCT-A) can be used to image vessels based on flow characteristics without any dye injection. Type 2 NV can be visualized using OCT-A with very typical patterns. A neovascular membrane appears as either a medusa-shaped complex or a glomerulus-shaped lesion in the outer retina and the choriocapillaris layer. Furthermore, in the choriocapillaris layer, the external borders of the lesion appear as a dark ring in most cases, and one or more central feeder vessels that extend deeply into the more profound choroidal layers are visible. Identification of type 2 NV is easily feasible for any clinician using OCT-A, especially in areas where there are normally no vessels, like in subretinal space, if the interpretation rules are respected.

Optical Coherence Tomography Angiography Features of Type 3 Neovascularization in Age-Related Macular Degeneration.

PURPOSE: To characterize the imaging features of type 3 neovascularization secondary to exudative age-related macular degeneration on optical coherence tomography (OCT) angiography (OCTA). METHODS: Patients diagnosed with treatment-naïve early-stage type 3 neovascularization underwent multimodal imaging, including color retinal photography or multicolor imaging, fluorescein angiography, indocyanine green angiography, spectral-domain OCT and OCTA. The OCTA features of type 3 neovascularization were analyzed and correlated with the findings on angiography and spectral-domain OCT. RESULTS: OCTA showed lesions characterized by a retinal-retinal anastomosis. These lesions emerged from the deep capillary plexus and formed a clear, tuft-shaped, high-flow network in the outer retinal segment in all eyes, abutting in the subretinal pigment epithelium space. In most cases, a small, clew-like lesion was present in the choriocapillaris segment. Moreover, in some cases, this clew-like lesion seemed to be connected to the choroid through a small-caliber vessel. CONCLUSION: OCTA of treatment-naïve type 3 neovascularization shows high-flow, tuft-shaped, abnormal outer retinal proliferation that is almost consistently associated with a small, clew-like lesion in the choriocapillaris layer.

Relating Retinal Morphology and Function in Aging and Early to Intermediate Age-related Macular Degeneration Subjects.

PURPOSE: To evaluate relationships between age-related macular degeneration (AMD) morphology on spectral-domain optical coherence tomography (SDOCT) and visual function. DESIGN: Cross-sectional, observational. METHODS: From the Alabama Study on Early AMD baseline visit, visual acuity, cone-mediated sensitivity, rod-mediated dark adaptation, and SDOCT were obtained in 1 eye per subject with no apparent retinal aging (n = 15), normal aging (n = 15), early AMD (n = 15), and intermediate AMD (n = 46). The volumes of retinal pigment epithelium (RPE)-drusen complex, RPE-drusen complex abnormal thinning, RPE-drusen complex abnormal thickening, and inner and outer retina were calculated in specified regions using semi-automated SDOCT segmentation. RESULTS: Better cone-mediated sensitivity was associated with greater RPE-drusen complex volume (r = 0.34, P < .001) and less RPE-drusen complex abnormal thinning volume (r = -0.31, P = .003). Longer rod-mediated dark adaptation time, the duration for rod-mediated sensitivity to recover from photo-bleach exposure, correlated with lower RPE-drusen complex volume (r = -0.34, P = .005) and greater RPE-drusen complex abnormal thinning volume (r = 0.280, P = .023). In 19 eyes with subretinal drusenoid deposits (SDD) vs 47 eyes without SDD, rod-mediated dark adaptation time was longer (mean ± SD 13.5 ± 7.0 vs 10.2 ± 3.1 minutes, P = .004), RPE-drusen complex abnormal thinning volume was greater (P < .0001), and visual acuity and cone sensitivity did not differ. CONCLUSION: Decreased function relates to structural markers on SDOCT in AMD. Because the RPE-drusen complex includes the interdigitation of outer segments and RPE apical processes and SDD in eyes with AMD, slower dark adaptation might be related to structural abnormalities of the RPE, the RPE-photoreceptor interface, or both.

Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age-Related Macular Degeneration.

Age-related macular degeneration continues to be the leading cause of severe central vision loss in older adults of European descent. Optical coherence tomography angiography (OCT-A) enables more accurate identification of type 1 neovascularization in age-related macular degeneration than traditional fluorescein and indocyanine green angiographies. In addition, OCT-A facilitates the morphological classification of type 1 lesions, including features characteristic of early, mature, and fibrotic lesions. Vessel complex analysis, including lesion area and capillary density quantification, can also be readily measured and monitored over time. Performing this analysis following anti-vascular endothelial growth factor therapy may lead to a better understanding of the efficacies and responses to such treatments. Although some limitations currently exist, OCT-A is a promising imaging modality that could prove to have profound implications if incorporated into regular clinical practice.

Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

PURPOSE: To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. METHODS: This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. RESULTS: Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. CONCLUSIONS: FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti-vascular endothelial growth factor therapy regardless of CNV lesion type.

Photoreceptor dysfunction in early and intermediate age-related macular degeneration assessed with mfERG and spectral domain OCT.

PURPOSE: To evaluate the changes of the photoreceptor layer (PRL) thickness with spectral domain optical coherence tomography (SD-OCT) and the retinal function by mfERG, as well as the correlation of morphology and function parameters in subjects with early and intermediate age-related macular degeneration (AMD). METHODS: Subjects with clinical diagnosis of early or intermediate AMD and age-matched healthy subjects were recruited prospectively in this study. Color fundus photography, SD-OCT, and mfERG were conducted. Retinal photoreceptor thickness was measured, and first-order kernel responses were recorded. The differences between AMD group and control group were compared, and the correlations between macular photoreceptor thickness and the mfERG were analyzed. RESULTS: PRL thickness (µm) in four areas including foveola and 0.5, 1.5, and 3 mm away from foveola was 192.48 ± 17.37, 163.73 ± 12.95, 130.93 ± 9.20, and 108.78 ± 7.81, respectively, in normal eyes, whereas in AMD group, they were 158.61 ± 45.25, 138.91 ± 20.92, 118.91 ± 12.85, and 95.00 ± 9.64, respectively (P < 0.001). The mean amplitude response densities of AMD patients decreased significantly compared to the control group in ring 1-6 (P < 0.001). The mean mfERG N1 and P1 latency of AMD patients prolonged compared to the control group, except the ring 1 (P = 0.588 and P = 0.084). The macular PRL thickness was significantly associated with the mfERGN1 and P1 amplitude density in ring 1-4 (r = 0.338-0.533, P < 0.01). CONCLUSIONS: PRL thickness decreases are in accordance with the deterioration of retinal electrophysiological activity. The retinal PRL thickness is important parameter to assess of early and intermediate AMD severity.

Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.

PURPOSE: To compare the ability of several visual functional tests in terms of the strength of their associations with the earliest phases of age-related macular degeneration (AMD), which bears on their potential to serve as functional endpoints in evaluating treatments for early AMD and prevention strategies. MATERIALS AND METHODS: Eyes from adults ≥60 years old were identified as being in normal macular health or in the earliest stages of AMD (steps 2, 3 or 4) through grading of color stereo-fundus photos by an experienced grader masked to all other study variables who used the 9-step Age-Related Eye Disease Study (AREDS) classification system for AMD severity. Visual function was assessed using the following tests: best-corrected visual acuity, low luminance visual acuity, spatial contrast sensitivity, macular cone-mediated light sensitivity and rod-mediated dark adaptation. RESULTS: A total of 1260 eyes were tested from 640 participants; 1007 eyes were in normal macular health (defined as step 1 in AREDS system) and 253 eyes had early AMD (defined as steps 2, 3 or 4). Adjusting for age and gender, early AMD eyes had two times the odds of having delayed rod-mediated dark adaptation than eyes in normal macular health (p = 0.0019). Visual acuity, low luminance acuity, spatial contrast sensitivity and macular light sensitivity did not differ between normal eyes and early AMD eyes. CONCLUSIONS: Eyes in the earliest phases of AMD were two times more likely to have delayed rod-mediated dark adaptation, as assessed by the rod-intercept, as compared to older eyes in normal macular health, whereas there was no difference in early AMD versus normal eyes in tests of visual acuity, low luminance acuity, macular light sensitivity and spatial contrast sensitivity.