Faculty Bibliography

PURPOSE/OBJECTIVE:To correlate structural changes of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) with patient age. DESIGN/METHODS:Retrospective study. SUBJECTS/METHODS:There were 50 eyes of 49 patients (age range 1-74 years) with CHRRPE studied at nine tertiary vitreoretinal institutions. METHODS:We analyzed the clinical findings with respect to lesion topography and pigmentation as well as investigated the optical coherence tomography (OCT) findings regarding the thickness, vitreoretinal interface, outer plexiform layer distortion, ellipsoid zone disruption and retinal pigment epithelium/Bruch's membrane complex involvement of CHRRPE. MAIN OUTCOMES/RESULTS:Clinical and imaging findings of CHRRPE at different ages. RESULTS:Analysis of 50 CHRRPE revealed younger patients were more likely to have partial thickness involvement of the retina (p = 0.009) with predominantly inner retinal layer involvement (p = 0.04). The inverse was true for older patients with CHRRPE. In addition, older patients more commonly showed pigmentary changes. Eyes with CHRRPE were more likely to have an increase in central macular thickness independently of tumor location. CONCLUSION/CONCLUSIONS:Based on these findings, we believe that CHRRPE typically begins in the inner retina and continues towards the outer retina over time, with increase in central macular thickness, despite the location of the tumor.

PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging (MMI) features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with macular neovascularization (MNV). DESIGN/METHODS:Retrospective, observational case series. METHODS:Fourteen eyes (14 patients, 7 male) were imaged with spectral-domain optical coherence tomography (OCT), and either fluorescein angiography or OCT angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity (BCVA) assessments. RESULTS:Mean age was 75±13 (range: 45-96) years, with mean follow-up duration of 27±21 (range: 1-56) months. Neovascular age-related macular degeneration (nAMD) was found in 71% (10/14) eyes. Type 2 MNV lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved following intravitreal anti-VEGF therapy in all eyes. Baseline BCVA improved from LogMar 0.84±0.32 (Snellen equivalent 20/138) to LogMar 0.48±0.31 (Snellen equivalent 20/60) at last follow-up, with treatment of the MNV. CONCLUSIONS:Type 2 MNV and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal anti-VEGF therapy results in rapid resolution of BDs and visual improvement in most eyes.

PURPOSE/OBJECTIVE:To evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes. METHODS:This retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes. RESULTS:Forty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy. CONCLUSION/CONCLUSIONS:Non-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.

PURPOSE/OBJECTIVE:To evaluate and compare para- and perilesional choriocapillaris vascular impairment in eyes with geographic atrophy (GA) with and without outer retinal tubulations (ORT). METHODS:Using swept source optical coherence tomography angiography (OCTA), 6x6mm scans of eyes with GA with and without ORT were acquired. Choriocapillaris en face flow and structural images were binarized, prior to flow signal deficit (FD) analysis in the para-atrophy zone (a 500 µm wide band adjacent to the GA) and the peri-atrophy zone (a 500 µm wide band adjacent to the latter). RESULTS:Twenty-four eyes of 19 patients with ORT and 18 eyes of 15 patients without ORT were analyzed. With and without ORT, mean percental area of FD (%FD) was greater in para- than in peri-atrophy zone. The difference of %FD between para- and peri-atrophy zone (deltaFD) was lower in eyes with ORT (mean 1.8477%, 95% CI 0.8607 to 2.8346) than without ORT (mean 4.0018%, 95% CI 2.8622 to 5.1414). CONCLUSION/CONCLUSIONS:In eyes with GA due to non-neovascular AMD, smaller reductions in FDs were found between the para- and peri-atrophy zone in eyes with ORT. In both cohorts, the para-atrophy zone had more FD than the peri-atrophy zone.

PURPOSE/OBJECTIVE:To describe a case of symptomatic outer retinal disruption in a patient heterozygous for the p.Leu154Pro interphotoreceptor matrix proteoglycan-1 (IMPG1) mutation implicated in adult-onset foveomacular vitelliform dystrophy. METHODS:Observational case report. RESULTS:We describe a case of a 25-year-old female patient with symptomatic scotoma and vision decrease who exhibited bilateral small foveal yellow spots. Optical coherence tomography revealed disorganization and decreased reflectance of the foveal ellipsoid and interdigitation zones in the left eye more than in the right eye. Fundus autofluorescence imaging showed minimal findings, and dye angiography was unrevealing. Multifocal electroretinogram revealed slightly decreased retinal sensitivity in the central retina of the left eye. Genetic testing identified a heterozygous p.Leu154Pro mutation in the IMPG1 gene. CONCLUSION/CONCLUSIONS:The p.Leu154Pro IMPG1 mutation may cause symptomatic outer retinal disturbance in the heterozygous state. Further studies are necessary.

PURPOSE/OBJECTIVE:To provide an image-based description of retinal features associated with risk for development of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD), as visualized with multimodal imaging anchored by structural optical coherence tomography. DESIGN/METHODS:Consensus meeting METHODS: As part of the Classification of Atrophy Meeting program, an international group of experts analyzed and discussed retinal multimodal imaging features in eyes with AMD associated with GA and/or risk of progression to GA. Attendees undertook pre-meeting grading exercises that were reviewed during the meeting sessions. Meeting presentations illustrated established and investigational multimodal imaging features and associated histology. These different features were then each discussed openly by the entire group to arrive at consensus definitions. These definitions were applied to 40 additional images that were graded independently by attendees, to further refine the consensus definitions and descriptions. RESULTS:Consensus was reached on images with descriptors for 12 features. These features included components of outer retinal atrophy (e.g., ellipsoid zone disruption), components of complete retinal pigment epithelium (RPE) and outer retinal atrophy (e.g., RPE perturbation with associated hypo- or hyper-transmission), features frequently seen in eyes with atrophy (e.g., refractile drusen) and features conferring risk for atrophy development (e.g., hyperreflective foci, drusen, and subretinal drusenoid deposits). CONCLUSIONS:An International consensus on terms and descriptions was reached on multimodal imaging features associated GA and with risk for GA progression in eyes with AMD. We believe this information will be useful to clinicians who manage patients with AMD, researchers who study AMD disease interventions and pathogenesis, and those who design clinical trials for therapies targeting earlier AMD stages than GA expansion.

PURPOSE/OBJECTIVE:To study microvascular characteristics of small resolved paracentral acute middle maculopathy (PAMM) lesions in fellow eyes of patients with unilateral retinal vein occlusion (RVO). DESIGN/METHODS:Prospective cross-sectional study. PARTICIPANTS/METHODS:Patients with prior unilateral branch or central RVO and optical coherence tomography (OCT) evidence of resolved PAMM in their fellow, otherwise normal, eyes were prospectively recruited and imaged with OCT angiography (OCTA). METHODS:The resolved PAMM lesions were identified as focal areas of inner nuclear layer thinning over an anteriorly displaced outer plexiform layer (OPL). En face OCTA projections showing the location and size of the resolved PAMM lesions were created using 2 OPL segmentation lines with -9 μm and 0 μm offsets, and the cumulative distribution was evaluated. Anterior to the resolved PAMM lesions, vessels in the superficial vascular plexus were traced to identify small arterioles supplying the affected areas. MAIN OUTCOME MEASURES/METHODS:Cumulative spatial distribution on small resolved PAMM lesions. RESULTS:From 24 fellow eyes of 24 patients with unilateral RVO (15 males and 9 females, mean age 62.0 ± 15.1 years) 152 resolved PAMM lesions were identified. Of these lesions, 130 (85.5%) were found within the perifoveal region, and only 12 (7.9%) were found within the temporal quadrant. Of 28 lesions analyzed, the arteriole supplying the affected area was a single side branch of a larger vessel, with only 3 supplied by a terminal branch. CONCLUSION/CONCLUSIONS:Small resolved PAMM lesions in fellow eyes of patients with unilateral RVO are most prevalent in perifovea regions supplied by side branches of low order retinal arteries.

Purpose:By optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia. Methods:In clinical OCT (61 eyes, 44 patients with AMD, 79.4 ± 7.7 years; 29 female; follow-up = 4.7 ± 0.9 years), one HRF type, RPE plume (n = 129 in 4 morphologies), was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy, 6; neovascular AMD, 3). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semiquantitatively by one observer (none, some cells, all cells). Results:Plume morphology evolved over time and many resolved (40%). Trajectories of RPE plume and cellular debris paralleled Müller glia, including near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Müller glia remained CRALBP positive. Plume cells approached and contacted retinal capillaries. Conclusions:HRF are indicators not predictors of overall disease activity. Gain and loss of function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial-mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.