Faculty Bibliography

PURPOSE/OBJECTIVE:To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of current literature and an analysis of retinal imaging. METHODS:We reviewed the literature for previous reports of BALAD. An analysis of retinal images was performed to support anatomic conclusions. RESULTS:A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Further, detachment of the entire layer of inner segments is a common postmortem artefact. We propose that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. CONCLUSION/CONCLUSIONS:Our review serves to strengthen the OCT nomenclature "bacillary layer detachment", based on specific reflectance information obtained by OCT and previously published histologic observations.

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:Macular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with anti-angiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histological analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD. DESIGN/METHODS:Case study and clinicopathologic correlation. SUBJECT/METHODS:A white woman in whom AMD findings of inactive subretinal fibrosis (right eye) were followed for 9 years using FAF and optical coherence tomography (OCT), with no detectable subretinal fluid or other recurrent exudation, and no intravitreal injections before death at age 90 years. METHODS:The right eye was preserved 6.25 hours after death, post-fixed in osmium tannic acid paraphenylenediamine, and prepared for sub-micrometer epoxy resin sections (n=115), with 19 matched to clinical OCT B-scans. MAIN OUTCOME MEASURES/METHODS:Light microscopic morphology of a hyperautofluorescent (hyperFAF) area attributed to prior exudation ("floodplain" hyperFAF), hypoautofluorescent (hypoFAF) spots of MA, and areas of unremarkable FAF. RESULTS:Floodplain hyperFAF was visible throughout the 9 years follow-up, with several hypoFAF atrophic spots expanding within it over time. The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic yet continuous RPE in histology. The hypoFAF spots inside the floodplain corresponded to complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on OCT and loss of both photoreceptors and RPE in histology. In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer. CONCLUSION/CONCLUSIONS:This direct clinicopathologic correlation for FAF imaging is the first for nAMD. FAF is a projection image that involves optical signal modulation by photoreceptors as well as emission signal sources in RPE. HyperFAF attributed to an exudative floodplain signifies loss of photoreceptors over continuous RPE. HypoFAF in MA signifies loss of both cell layers. FAF imaging should be interpreted with the multilayer perspective provided by OCT for maximal value. Prevention of exudation in nAMD may preserve photoreceptors.

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.