Prevalence, Features, and Outcomes of Type 1 Neovascularization in Eyes with Angioid Streaks.

PURPOSE: 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: Retrospective longitudinal cohort study. PARTICIPANTS: 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: 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): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

THE PROGNOSTIC SIGNIFICANCE OF ACUTE HENLE FIBER LAYER HYPERREFLECTIVITY IN PLACOID DISEASES.

PURPOSE: To investigate the pathophysiology and prognostic significance of acute Henle fiber layer (HFL) hyperreflectivity in placoid diseases by examining its relationship with impaired choroidal flow and persistent photoreceptor disruption. METHODS: Retrospective-prospective observational study on patients with placoid diseases. Indocyanine green angiography and optical coherence tomography were performed during the acute phase and follow-up. Impaired choroidal flow, HFL hyperreflectivity, and persistent ellipsoid zone disruption, their colocalization index, and their associations with initial and final visual acuity were explored. RESULTS: Sixteen eyes from eight patients (mean age, 25.3 ± 6.44 years) were included (median follow-up, 13.5 months). Quantitative analysis revealed significant correlations between areas of impaired choroidal flow, HFL hyperreflectivity, and persistent ellipsoid zone disruption (correlation coefficients of 0.69, 0.63, and 0.46, respectively). Impaired choroidal flow area exceeded HFL hyperreflectivity (P = 0.002) and ellipsoid zone disruption (P = 0.003). A noteworthy 94% nonrandom overlap between HFL hyperreflectivity and ellipsoid zone disruption was observed. Worse initial visual acuity correlated with foveal involvement (P = 0.0002), thicker choroid (P = 0.001), larger impaired choroidal flow areas (P = 0.02), and thinner outer retina post lesion inactivation (P = 0.04). CONCLUSION: Henle fiber layer hyperreflectivity predicted photoreceptor recovery potential in placoid diseases. If HFL hyperreflectivity corresponds to acute HFL damage, it may suggest more severe involvement of the entire photoreceptor length.

ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY AND PLACOID VARIANT DISEASES MASQUERADING AS AGE-RELATED MACULAR DEGENERATION IN THE ELDERLY: A Case Series.

PURPOSE: To report eight cases of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or persistent placoid maculopathy (PPM) initially masquerading as age-related macular degeneration in elderly individuals. METHODS: APMPPE or PPM eyes in patients above age 55 years with macular retinal pigment epithelium disruption including drusenoid lesions on macular examination and/or with multimodal imaging were included. At least one method of multimodal imaging including fluorescein angiography (FA), indocyanine green angiography, optical coherence tomography (OCT), and OCT angiography (OCTA) was performed in all eyes for diagnosis and to monitor for macular neovascularization. RESULTS: Eight elderly male patients presented with vision loss and were all initially diagnosed with non-neovascular or neovascular age-related macular degeneration. With the aid of multimodal retinal imaging, a final diagnosis of either APMPPE or PPM was rendered. With FA and indocyanine green angiography, choroidal hypoperfusion was detected in all but one eye. With OCT, the angular sign of Henle fiber layer hyperreflectivity was identified in >50% of eyes. With OCTA, inner choroidal flow deficits were detected in all eyes. Macular neovascularization requiring anti-vascular endothelial growth factor injection therapy complicated three of eight cases. CONCLUSION: Both APMPPE and PPM may develop in elderly individuals and may masquerade as age-related macular degeneration on presentation. Multimodal imaging including FA, indocyanine green angiography, and OCTA are important diagnostic modalities to assess for inner choroidal hypoperfusion to arrive at an accurate diagnosis and to detect macular neovascularization, which frequently complicates APMPPE and PPM. In these patients, serial anti-vascular endothelial growth factor intravitreal injections are essential in treating macular neovascularization and in preventing significant vision loss.

Dosing vs Assessment Intervals With Faricimab and Aflibercept.

This Viewpoint highlights the discrepancy between dosing and patient assessment schedules in clinical trials for 2 new intravitreal agents, faricimab, 6 mg, and aflibercept, 8 mg, to treat neovascular age-related macular degeneration.

Central Bouquet Hemorrhages in Pathologic Myopia: Clinical Characteristics and Prognostic Relevance.

PURPOSE: To compare the clinical implications of central bouquet hemorrhages (CBHs) to primarily subretinal hemorrhages, both occurring in the setting of pathologic myopia with lacquer crack formation. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: Twenty-five eyes (11 primarily subretinal hemorrhages and 14 CBH) were monitored over a median of 35 (interquartile range [IQR], 9.50-54) months. MAIN OUTCOMES MEASURES: Comprehensive ophthalmic examinations and OCT were reviewed. The study employed linear mixed-effects models to compare the impact of CBH versus primarily subretinal hemorrhages on baseline visual acuity (VA), rate of VA improvement, and final VA, adjusting for the follow-up period. Times of hemorrhages reabsorbtion and rate of ellipsoid zone (EZ) layer disruption on OCT were recorded. RESULTS: Eyes with CBH exhibited significantly worse baseline VA (0.93 ± 0.45 logarithm of the minimum angle of resolution [logMAR]; 20/160 Snellen vs. 0.36 ± 0.26 logMAR [20/50 Snellen], P < 0.001), a slower rate of VA improvement (P = 0.04), and a trend toward worse final VA (0.48 ± 0.47 logMAR [20/60 Snellen] vs. 0.16 ± 0.16 logMAR [20/30 Snellen], P = 0.06) compared with eyes with primarily subretinal hemorrhages. The CBH group experienced longer median reabsorption times (10 [IQR, 4.6-23.3] months vs. 2.3 [IQR, 2-3.2] months), and a higher prevalence of EZ layer disruption (86% vs. 0%), than the group with primarily subretinal hemorrhages. Central bouquet hemorrhage reabsorption was followed by the appearance of vertical hyperreflective lines in the central fovea in 67% of eyes, persisting for up to 6 years of follow-up. CONCLUSIONS: Central bouquet hemorrhage signifies a distinct condition in pathologic myopia, characterized by worse visual outcomes, prolonged structural impact, and possible irreversible damage, compared with primarily subretinal hemorrhages. Central bouquet hemorrhage regression should be taken into account in the differential diagnosis of vertical hyperreflective lesions in the central fovea on OCT in eyes with pathologic myopia. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD: From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS: From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION: The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH SEVERE PLASMODIUM FALCIPARUM MALARIA.

PURPOSE: To report a case of bilateral paracentral acute middle maculopathy lesions on spectral domain-optical coherence tomography(OCT) secondary to severe Plasmodium falciparum malaria. METHODS: Retrospective case report. Spectral domain-OCT, ultra-widefield fluorescein angiography, and OCT angiography were performed and analyzed. RESULTS: A 54-year-old healthy man presented with acute vision loss in both eyes few days after being diagnosed with severe Plasmodium falciparum malaria. Ophthalmoscopic examination was unremarkable, but near-infrared reflectance imaging showed patchy hyporeflective areas located at the terminal tips of the venous branches. Corresponding spectral-domain OCT demonstrated alternating bands of hyperreflectivity involving the inner nuclear layer, consistent with skip paracentral acute middle maculopathy lesions. Optical coherance tomography angiography illustrated corresponding flow signal loss at the level of the deep capillary plexus. Ultra-widefield fluorescein angiography showed peripheral retinal vein staining and capillary nonperfusion. CONCLUSION: Paracentral acute middle maculopathy may be an OCT manifestation of malarial retinopathy associated with severe Plasmodium falciparum infection.

CENTRAL BOUQUET HEMORRHAGE: Clinical and Multimodal Imaging Features.

PURPOSE: To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage." METHODS: Retrospective, observational, multicenter case series of eyes with central bouquet hemorrhage. Multimodal imaging features were reviewed and analyzed. RESULTS: Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6 ± 21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia Type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with central bouquet hemorrhage displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer. Cross-sectional optical coherence tomography showed a well-delineated round hyperreflective lesion involving the central foveal Henle fiber layer/outer nuclear layer in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented Henle fiber layer were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36). CONCLUSION: "Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with Henle fiber layer hemorrhage and encountered in a spectrum of macular disease.

INFLAMMATORY CELL ACTIVITY IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Histologic Case Study.

BACKGROUND: Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration. METHODS: Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes. RESULTS: Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells. CONCLUSION: Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.

PUNCTATE INNER PACHYCHOROIDOPATHY: Demographic and Clinical Features of Inner Choroidal Inflammation in Eyes with Pachychoroid Disease.

PURPOSE: To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes. METHODS: Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences. RESULTS: Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters. CONCLUSION: While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.

MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR?

PURPOSE: To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy. METHODS: Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed. RESULTS: Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy. CONCLUSION: Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy .

Latest advances in white spot syndromes: New findings and interpretations.

White spot syndromes (WSS) pose challenges in the field of ophthalmology, particularly in terms of accurate diagnosis and effective management. However, recent advancements in multimodal imaging (MMI) have significantly contributed to our understanding of WSS, allowing for improved characterization of these inflammatory chorioretinopathies. By employing various imaging modalities, including fundus fluorescein angiography, indocyanine green angiography, fundus autofluorescence, optical coherence tomography (OCT), ultra-widefield imaging, and OCT angiography, researchers and clinicians have gained valuable insights into the underlying pathophysiological changes and clinical progression of WSS. Furthermore, MMI has unveiled novel and atypical variants within the spectrum of WSS, expanding our knowledge in this field. Notably, the identification of secondary forms of WSS occurring concurrently with unrelated chorioretinal disorders has suggested a potential autoimmune mechanism underlying these conditions. The introduction of MMI has also facilitated a more comprehensive evaluation of previously ill-defined entities, such as acute zonal occult outer retinopathy, leading to improved diagnostic criteria and enhanced recognition of distinct features. This review paper provides a comprehensive overview of the latest advances and interpretations in WSS. By integrating MMI into the diagnosis and management of these conditions, this review aims to enhance patient outcomes and provide valuable insights into the complexities surrounding WSS.

Cavitary Choroidal Nevus Showing Thickness Fluctuations in Response to Anti-VEGF Therapy for Diabetic Macular Edema: A Case Report.

PURPOSE: To report the multimodal imaging features of a cavitary choroidal nevus showing thickness fluctuations that mirrored the response of diabetic macular edema (DME) to intravitreal anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), fluorescein (FA) and indocyanine green angiography (ICGA), OCT-angiography (OCTA), and B-scan ultrasonography were analyzed. RESULTS: A female in her 80s with a cavitary choroidal nevus and DME was treated with intravitreal anti-VEGF therapy using a pro re nata regimen over 5 years. The choroidal nevus showed thickness fluctuations paralleling the response of DME to anti-VEGF therapy. Worsening of the DME was associated with marked increased choroidal lesion thickness on OCT. Conversely, resolution of DME after intravitreal anti-VEGF injections was followed by choroidal lesion flattening on OCT. Variations of the choroidal lesion thickness were mainly dependent on changes of intralesional hyporeflective caverns on OCT. CONCLUSION: Our report shows thickness variations of a cavitary choroidal nevus that paralleled the clinical course of DME treated with intravitreal anti-VEGF therapy. To the best of our knowledge, this is the first report on volume variations of a cavitary choroidal nevus following anti-VEGF therapy.