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Purpose: To report visual outcomes and rate of retinal pigment epithelium (RPE) atrophy progression in patients with extensive macular atrophy with pseudodrusen-like appearance (EMAP).Design: Retrospective, observational study.Participants: Patients with EMAP and symptom onset before 55 years of age, at least 12 months of followup using Spectralis blue-light fundus autofluorescence (BAF) and OCT and with no other ocular or systemic conditions.Methods: Best-corrected visual acuity (BCVA), BAF, and OCT images were reviewed at baseline and at each annual visit until the last available follow-up. Atrophy was measured by 2 graders using the region finder software on Heidelberg Explorer and confirmed using OCT scans covering the entire atrophic lesion. The following imaging biomarkers were analyzed at each visit: foveal atrophy, vitreomacular traction, outer retinal tubulations, choroidal caverns and subfoveal choroidal thickness, border autofluorescence pattern (hyper-autofluorescent or isoautofluorescent), and border irregularity as expressed by circularity index (CI).Main Outcome Measures: Primary outcomes were annual rate of atrophy enlargement and BCVA loss in EMAP patients. Secondary outcomes included the assessment of potential factors able to predict disease progression.Results: Thirty-six eyes from 18 patients with EMAP (6 men [33%]; mean age at symptom onset, 48.1 AE 1.7 years) were included. Mean follow-up lasted 32.8 AE 14.3 months. RPE atrophy increased from 10.8 AE 6.3 mm 2 at baseline to 18.1 AE 8.3 mm 2 at the end of follow-up, with a rate of 2.91 AE 1.09 mm 2 /year. Faster progression was associated with smaller CI at baseline (P ¼ 0.02) and with iso-autofluorescent lesion borders (P ¼ 0.01). Visual acuity declined progressively at a rate of 7.4 AE 5.8 letters per year, with 57% of eyes showing vision of 20/ 200 Snellen or worse at the 4-year follow-up. Worse visual outcomes were observed in patients with early foveal involvement at baseline (P ¼ 0.02).Conclusions: Patients affected by EMAP present a rapid expansion of RPE atrophy that is comparable with the diffuse-trickling form of geographic atrophy. More irregular and iso-autofluorescent lesion borders seem to predict faster progression. Our findings may provide relevant information for patient counseling and future interventional approaches to select the best candidates and proper clinical outcomes. Ophthalmology

Purpose To evaluate a novel deep learning algorithm to distinguish between eyes that may or may not have a graft detachment based on pre–Descemet membrane endothelial keratoplasty (DMEK) anterior segment optical coherence tomography (AS-OCT) images. Methods Retrospective cohort study. A multiple-instance learning artificial intelligence (MIL-AI) model using a ResNet-101 backbone was designed. AS-OCT images were split into training and testing sets. The MIL-AI model was trained and validated on the training set. Model performance and heatmaps were calculated from the testing set. Classification performance metrics included F1 score (harmonic mean of recall and precision), specificity, sensitivity, and area under curve (AUC). Finally, MIL-AI performance was compared to manual classification by an experienced ophthalmologist. Results In total, 9466 images of 74 eyes (128 images per eye) were included in the study. Images from 50 eyes were used to train and validate the MIL-AI system, while the remaining 24 eyes were used as the test set to determine its performance and generate heatmaps for visualization. The performance metrics on the test set (95% confidence interval) were as follows: F1 score, 0.77 (0.57–0.91); precision, 0.67 (0.44–0.88); specificity, 0.45 (0.15–0.75); sensitivity, 0.92 (0.73–1.00); and AUC, 0.63 (0.52–0.86). MIL-AI performance was more sensitive (92% vs. 31%) but less specific (45% vs. 64%) than the ophthalmologist's performance. Conclusions The MIL-AI predicts with high sensitivity the eyes that may have post-DMEK graft detachment requiring rebubbling. Larger-scale clinical trials are warranted to validate the model. Translational Relevance MIL-AI models represent an opportunity for implementation in routine DMEK suitability screening.

Background: To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Methods: Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain-optical coherence tomography, short-wavelength autofluorescence and 10-2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye.Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAF 8 ).Results: Thirty-nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAF 8 was positively correlated with age (p = 0.004). Although HCQ patients showed a higher mean qAF 8 compared with untreated subjects (294.7 ± 65.3 vs. 268.9 ± 57.5), the difference was not significant (p = 0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared with untreated subjects (all p < 0.05).Conclusions: These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.Mariano Cozzi shared first authorship.

Purpose: To investigate the influence of age, gender, and underlying disease on the optical coherence tomography (OCT) features of choroidal neovascularization (CNV) secondary to inflammation, myopia (mCNV), and age-related macular degeneration (AMD-CNV). Methods: Demographic and clinical data of eyes with treatment-naive inflammatory CNV, mCNV, and Type 2 AMD-CNV were collected. Optical coherence tomography images were reviewed to determine the presence of pitchfork sign, pigment epithelial detachment, subretinal fluid (SRF), intraretinal cysts, subretinal hyperreflective material, atrophy, and outer retinal disruption graded 1 to 4. The influence of demographics and underlying etiology on OCT signs was investigated. Results: One hundred and eighty-five eyes from 179 patients were enrolled. The mean [SD] age was 36 [±14.4], 62 [±18], and 77 [±8] for the inflammatory CNV, mCNV, and AMD-CNV, respectively (P < 0.001). Multiple linear regression showed that the presence of pitchfork sign was negatively associated with age (P < 0.0001), regardless of underlying disease. By contrast, the SRF, pigment epithelial detachment, intraretinal cysts, and the outer retinal disruption were all positively influenced by age, regardless of gender and underlying disease (all P < 0.01). Logistic regression showed that none of the OCT signs increased the likelihood for diagnosis of inflammatory CNV. By contrast, the absence of SRF was suggestive for mCNVs, and the presence of pigment epithelial detachment and SRF was suggestive for AMD-CNVs. Conclusion: The age of the patient had a significant effect on the OCT appearance of the CNV, particularly the presence of a pitchfork sign, regardless of the underlying etiology. The absence of SRF was suggestive for a diagnosis of mCNVs. The presence of SRF and pigment epithelial detachment was suggestive for AMD-CNVs.

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Background: To compare four different optical coherence tomography (OCT) devices for visualization of retinal and subretinal layers in highly myopic eyes. Methods: In this prospective, observational, cross-sectional study, consecutive patients with high myopia and control subjects were imaged by four OCT devices: Spectralis OCT2, PlexElite 2.0 100 kHz, PlexElite 2.0 200 kHz and the Canon Xephilio OCT-S1. The acquisition protocol for comparison consisted of single vertical and horizontal line scans centered on the fovea. Comparison between the devices in the extent of visible retina, presence of conjugate image or mirror artifacts, visibility of the sclerochoroidal interface and retrobulbar tissue. Results: 30 eyes with high myopia and 30 control subjects were analyzed. The visualized RPE length was significantly different between the OCT devices with Xephilio OCT-S1 imaging the largest extent (p < 0.0001). The proportion of eyes with conjugate image artifact was significantly higher with the Spectralis OCT (p < 0.0001), and lower with the PlexElite 200 kHz (p < 0.0001). No difference in visibility of the sclerochoroidal interface was noted among instruments. The retrobulbar tissue was visible in a higher proportion of eyes using swept-source PlexElite 100 kHz and 200 kHz (p < 0.007) compared to the other devices. Conclusions: In highly myopic eyes, the four OCT devices demonstrated significant differences in the extent of the retina imaged, in the prevalence of conjugate image artifact, and in the visualization of the retrobulbar tissue.