Faculty Bibliography

PURPOSE/OBJECTIVE:This study aimed to delineate the characteristics, prevalence, and outcomes of neovascularization (NV), particularly aneurysmal type 1 NV, in patients with angioid streaks (AS) secondary to pseudoxanthoma elasticum (PXE), and to introduce a clinical classification based on multimodal imaging. DESIGN/METHODS:Retrospective longitudinal cohort study. PARTICIPANTS/METHODS:Eighty-five patients (168 eyes) with AS secondary to PXE at 2 tertiary referral centers. METHODS:Data collection included demographic, medical, and ocular histories. Diagnostic methods comprised fundus photography, autofluorescence, indocyanine green angiography, OCT, and OCT angiography. MAIN OUTCOME MEASURES/METHODS:Prevalence of type 1 NV, visual acuity (VA), risk of exudation. RESULTS:Type 1 NV was identified in 127 eyes (76%), with 85 of these (67%) showing exclusively type 1 NV. These lesions often originated around the disc, at sites of Bruch membrane dehiscences, and followed the path of AS, extending to the macula in 101 eyes (80%). Despite 65% of type 1 NV remaining nonexudative, 35% evolved into exudative over 5 years, and 11 eyes experienced midperipheral subretinal hemorrhages. Aneurysmal dilations, observed in 57% of eyes, substantially increased exudation risk (hazard ratio = 3.86, P = 0.02). Despite treatment, VA significantly deteriorated in exudative type 1 NV (P = 0.02). Type 2 NV, detected in 42 eyes (33%), often coexisted with type 1 NV and was associated with poorer visual outcomes and higher rates of macular atrophy. A classification of AS was developed, ranging from empty AS (stage 0, no NV) to advanced NV (stage 3, both type 1 and type 2 NV). CONCLUSIONS:Type 1 NV predominates in AS. Although predominantly nonexudative, its progression correlates with substantial visual impairment, similar to the deficits observed with type 2 NV. Aneurysmal type 1 NV poses a significant exudation risk, underscoring the need for vigilant monitoring. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

We report clinical and imaging features of Valsalva-induced choroidal hemorrhage (VICH) in high myopia, highlighting choroidal venous congestion, and hyperpermeability in dominant vortex vein systems, and luminal compression at the crest of deep myopic staphylomas.

OBJECTIVE:To develop a consensus nomenclature for Optical Coherence Tomography Angiography (OCTA) findings in retinal vascular diseases (RVD). DESIGN/METHODS:Expert consensus using standardized online surveys with modified Likert scale. PARTICIPANTS/METHODS:RVD imaging experts, OCT biomedical engineers and the members of the International Retinal Imaging Society (IntRIS) METHODS: A PubMed literature review identified quantitative and qualitative terms forming the basis for a consensus-building process using a modified Delphi method. Agreement levels were categorized as "Accepted" (median ≥ 6), "Considerable Consensus" (median 6-7, IQR ≤ 3), "Strong Consensus" (median ≥ 8, IQR ≤ 2), and "Refined Strong Consensus" (median ≥ 8, IQR ≤ 2, with ≥ 70% responses in the 8-10 range). A multidisciplinary expert panel refined the terminology through three survey rounds, leading to a final survey conducted by IntRIS members. MAIN OUTCOME MEASURES/METHODS:Consensus on OCTA nomenclature in RVD RESULTS: The literature review identified 58 relevant papers, yielding 51 quantitative and 108 qualitative terms. A series of three surveys was used to refine the nomenclature framework for describing OCTA findings. The selected framework includes a generic term ("OCTA signal"), adjective terms ("presence/absence", "decreased/increased", "normal/abnormal"), and descriptive/etiologic terms ("of unknown cause", "due to blockage", "due to non-perfusion"). In the final survey among 44 IntRIS members, the framework achieved strong consensus for overall acceptance (median: 8.0, IQR: 7.0-9.0). The term "OCTA signal" met refined strong consensus criteria (median: 8.0, IQR: 8.0-9.0, with ≥ 70% of responses in the 8-10 range). Adjective terms, including "absence/presence" and "increased/decreased," were also rated with strong consensus (median: 8.0, IQR: 7.0-9.0). Similarly, descriptive/etiologic terms achieved strong consensus (median: 8.0, IQR: 7.0-9.0). Adoption of the framework for clinical practice and scientific reporting was rated with strong consensus (clinical: median 8.0, IQR: 7.0-9.0; scientific: median 9.0, IQR: 8.5-10.0). CONCLUSIONS:This study establishes a strong consensus framework for reporting OCTA findings in RVD for clinical and scientific contexts.

PURPOSE/UNASSIGNED:The purpose of this study was to develop ground-truth histology about contributors to variable fundus autofluorescence (FAF) signal and thus inform patient selection for treating geographic atrophy (GA) in age-related macular degeneration (AMD). METHODS/UNASSIGNED:One woman with bilateral multifocal GA, foveal sparing, and thick choroids underwent 535 to 580 nm excitation FAF in 6 clinic visits (11 to 6 years before death). The left eye was preserved 5 hours after death. Eye-tracked ex vivo imaging aligned sub-micrometer epoxy resin sections (n = 140, 60 µm apart) with clinic data. Light microscopic morphology corresponding to FAF features assessed included drusen-driven atrophy, persistent hyperautofluorescence (hyperFAF) islands and peninsulas within atrophy, and hyperFAF and hypoautofluorescence (hypoFAF) inner junctional zone (IJZ) and outer junctional zone (OJZ) relative to descent of external limiting membrane (ELM). Atrophy growth rate was calculated. RESULTS/UNASSIGNED:HypoFAF atrophic spots appeared in association with drusen, and then expanded and coalesced. Over drusen (n = 45, all calcified), RPE was continuous and thin, photoreceptors were short or absent, and initially intact ELM descended where RPE was absent. In persistent hyperFAF within atrophy and in the OJZ, the RPE was continuous and dysmorphic, photoreceptors were present and short, and BLamD was thick. In the IJZ, mottled FAF corresponded to dissociated RPE atop persistent BLamD. Overall linear growth rate (0.198 mm/ year) typified multifocal GA. CONCLUSIONS/UNASSIGNED:FAF in GA is locally multifactorial, with photoreceptor shortening potentially promoting hyperFAF by increasing incoming excitation light available to RPE fluorophores. RPE dysmorphia may lead to either longer or shorter pathlength for excitation light. At both atrophy initiation and expansion Müller glia are major participants.

PURPOSE/OBJECTIVE:To report the multimodal imaging features of hyperpigmented chorioretinal lesions originating from the retinal pigment epithelium (RPE) within punched-out lesions of punctate inner choroidopathy (PIC). METHODS:Retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), and OCT-angiography (OCTA) were analyzed. RESULTS:A 49-year-old female with myopic degeneration developed progressive lesions of PIC requiring immunosuppressive therapy with adalimumab. Within areas of punched-out chorioretinal atrophic lesions, the occurrence of hyperpigmented lesions were observed which enlarged and extended into the choroid over a multiyear follow-up. CONCLUSION/CONCLUSIONS:This case illustrates the development of pigmented choroidal lesions appearing to originate from the RPE through transdifferentiation following previous chorioretinal inflammatory lesions. The introduction of adalimumab treatment may have activated the cellular migration of the RPE. To the best of our knowledge, this is the first report of intrachoroidal RPE migration in PIC.

Type 3 macular neovascularization (MNV) is a unique form of neovascular age-related macular degeneration (AMD) that presents distinct pathogenetic features, clinical manifestations, and prognostic considerations when compared to types 1 and 2 MNV. Insights gained from clinicopathological correlations, bridging in vivo examination techniques with ex vivo histological analysis, have significantly enhanced our comprehension of this MNV phenotype, shaped current management strategies and influenced future directions for therapeutics. The particularities of type 3 MNV, which may largely stem from its origin from the retinal vasculature, are critically important for predicting the disease course. Our current understanding suggests that type 3 MNV occurs in response to retinal pigment epithelium (RPE) disruption and photoreceptor loss when neovessels originating from the deep capillary plexus are accompanied by activated Müller glia as they infiltrate sub-retinal pigment epithelium basal laminar deposits. Dysregulation of angiogenic and angiostatic factors are thought to play a key role in its pathogenesis. The prognosis for type 3 MNV is likely bilateral involvement and progression towards macular atrophy. It may be imperative for practitioners to distinguish type 3 MNV from other mimicking pathologies such as intraretinal microvascular anomalies, which are also part of the type 3 disease spectrum. For instance, deep retinal age-related microvascular anomalies (DRAMA) may present with similar features on multimodal imaging yet may necessitate distinct management protocols. Distinguishing between these conditions may be vital for implementing tailored treatment regimens and improving patient outcomes in the diverse landscape of AMD phenotypes in the future.

PURPOSE/UNASSIGNED:Abetalipoproteinemia (ABL, MIM 200,100) is a rare autosomal recessive disorder caused by nonfunctional microsomal triglyceride transfer protein leading to absence of apolipoprotein B-containing lipoproteins in plasma and a retinitis pigmentosa-like fundus. The MTTP gene is expressed in retinal pigment epithelium (RPE) and ganglion cells of the human retina. Understanding ABL pathophysiology would benefit from new cellular-level clinical imaging of affected retinas. METHODS/UNASSIGNED:We report multimodal retinal imaging in two patients with ABL. Case 1 (67-year-old woman) exhibited a bilateral decline of vision due to choroidal neovascularization (CNV) associated with angioid streaks and calcified Bruch membrane. Optical coherence tomography were consistent with basal laminar deposits and subretinal drusenoid deposits (SDD). RESULTS/UNASSIGNED:Case 2 (46-year-old woman) exhibited unusual hyperpigmentation at the right fovea with count-fingers vision and a relatively unremarkable left fundus with 20/30 vision. The left eye exhibited the presence of nodular drusen and SDD and the absence of macular xanthophyll pigments. CONCLUSION/UNASSIGNED:We propose that mutated MTTP within the retina may contribute to ABL retinopathy in addition to systemic deficiencies of fat-soluble vitamins. This concept is supported by a new mouse model with RPE-specific MTTP deficiency and a retinal degeneration phenotype. The observed range of human pathology, including angioid streaks, underscores the need for continued monitoring in adulthood, especially for CNV, a treatable condition.