Retinal Ischemic Perivascular Lesions are associated with myocardial infarction in patients with coronary artery disease.

PURPOSE: To evaluate the association of retinal ischemic perivascular lesions (RIPLs) with myocardial infarction (MI) among patients diagnosed with coronary artery diseases (CAD). DESIGN: Retrospective cross-sectional study. METHODS: Consecutive patients (317 patients) with CAD who underwent macular spectral domain optical coherence tomography (SD-OCT) were captured. Patients with CAD who developed MI were compared to those without MI. SD-OCT were reviewed by two independent and masked graders for the presence of RIPLs. Medical records were reviewed. Multivariate logistic regression analysis was used to evaluate the relationship between RIPLs and MI including the following covariates age, gender, smoking status, hypertension, diabetes, dyslipidemia and body mass index. RESULTS: Of 317 patients with CAD for whom OCT scans were available to study, there were 54 (17%) with a history of MI. A higher prevalence of RIPLs was observed in the MI group compared to the non-MI group (59.3% vs. 35.7%; p<0.001). Presence of RIPLs was significantly associated with MI with an odds ratio of 3 (1.91-4.74; p<0.001), after adjusting for age, gender, smoking status, hypertension, diabetes, dyslipidemia and body mass index. CONCLUSION: The presence of RIPLs, detected with SD-OCT, is significantly associated with MI in patients with CAD. These findings underscore the potential clinical utility of incorporating RIPL evaluation in the medical management of CAD.

Systemic and ocular outcomes in patients with young-onset type 2 diabetes.

PURPOSE: To analyze the systemic and ocular outcomes in patients with young-onset type 2 diabetes (YO-DM2) based on grade of presenting diabetic retinopathy (DR). METHODS: Retrospective cohort study analysis of empaneled patients with type 2 diabetes <40 years old with retinopathy screening within the Los Angeles Department of Health Services between 01/01/2017-07/01/2021 were included. Patients were stratified based on presenting severity of DR determined on fundus photographs or clinical examination. Patient's systemic co-morbidities and ocular outcomes were then compared across each group. Procedural (e.g. intravitreal injections) and surgical interventions (e.g. pars plana vitrectomy) were documented as performed by the treating physician. RESULTS: 2795 patients were screened from 12,456 patients diagnosed with diabetes younger than age 40 (22.4 %). Of these, 1496 patients were diagnosed with type 2 DM. 1084 (72.4 %) of patients presented without DR, 307 (20.5 %) presented with non-proliferative diabetic retinopathy (NPDR), and 105 (7.0 %) of patients presented with proliferative diabetic retinopathy (PDR). Increasing presenting diabetic retinopathy severity was associated with longer duration of diabetes, greater systemic comorbidities (e.g. diabetic foot disease, neuropathy, chronic kidney or end stage renal disease), worse baseline and final visual acuity, and required more procedural and surgical interventions. CONCLUSIONS: Worse presenting DR severity in patients young-onset type 2 diabetes was associated with greater comorbid systemic and ocular disease with worse visual acuity outcomes. <1 % of patients without diabetic retinopathy or with mild NPDR were likely to progress to PDR. Diabetic kidney disease was an independent risk factor for developing neovascular glaucoma and retinal detachments. Prompt evaluation and intervention in patients with YO-DM2 may help reduce the associated systemic and ocular morbidity.

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.

OCT Grading System of Macular Infarction Predicts Vision in Participants With Central Retinal or Hemiretinal Vein Occlusion: A Secondary Analysis of SCORE2.

PURPOSE: To determine whether macular infarction measured as hyper-reflectivity of the middle and inner retinal layers predicts long-term visual acuity outcomes in participants with central retinal vein occlusion (CRVO) or hemi-retinal vein occlusion (HRVO). DESIGN: Clinical cohort study using post hoc secondary analysis of phase 3 clinical trial data. METHODS: This post hoc secondary analysis of the phase 3 Study of COmparative Treatments for REtinal Vein Occlusions 2 (SCORE2) clinical trial included 310 of the 362 participants with macular edema secondary to CRVO/HRVO who were randomized to injections of aflibercept or bevacizumab. Month 01 (M01) optical coherence tomography (OCT) images were analyzed using the following grading scheme: no infarction (grade 0), only middle retinal infarction (grade 1), diffuse middle and patchy inner retinal infarction (grade 2), and diffuse middle and inner retinal infarction (grade 3). Visual acuity letter score (VALS), central subfield thickness (CST), and number of anti-vascular endothelial growth factor (anti-VEGF) injections were correlated with the infarction severity grade at month 01. RESULTS: More severe macular infarction, with both middle and inner retinal layer hyper-reflectivity (ie, grades 2 and 3), was associated with worse M00 VALS and was predictive of VALS at M01 to M60 (P < .001). More severe infarction was associated with greater CST at presentation; however, after the first anti-VEGF injection, CST decreased and was similar across all grades at all time points (P > .05) with similar number of injections. CONCLUSIONS: Participants with more severe macular infarction at M01, as graded with OCT, exhibited worse visual outcomes despite significantly improved macular edema from month 6 to 5 years. This suggests that macular infarction may drive visual acuity after retinal fluid is treated with anti-VEGF.

Pachyvitelliform maculopathy: an optical coherence tomography analysis of a novel entity.

PURPOSE: To describe the optical coherence tomography features of pachyvitelliform maculopathy (PVM), an acquired vitelliform lesion (AVL) associated with pachychoroid disease. METHODS: This study was a retrospective, multicentre, observational analysis.Medical records and multimodal imaging were reviewed in all patients with pachychoroid disease and AVL. Visual acuity, central choroidal thickness (CCT), AVL dimensions, total choroidal area, luminal choroidal area, stromal choroidal area and choroidal vascular index were measured in all eyes with PVM and compared with normal age-matched control eyes. RESULTS: Mean age of the PVM group (17 eyes of 17 patients) was 71.41 years. Average follow-up was 33.15 months. Baseline VA was 20/40 in the PVM group and declined to 20/100 (p=0.006). AVLs were all detected overlying pachyvessels with optical coherence tomography and were all hyperautofluorescent with fundus autofluorescent imaging. Mean CCT in the PVM group was significantly greater (352.35 µm) than the CCT in the control group (226.88 µm, p<0.001). Retinal pigment epithelium (RPE) disruption was present in 64.71% of eyes with PVM at baseline and 41.18% developed macular atrophy at the end of follow-up. CONCLUSIONS: PVM, defined by the presence of AVL associated with pachychoroid features, is a distinct novel entity of the pachychoroid disease spectrum. This study suggests a possible pathogenesis of RPE dysfunction secondary to a thick choroid, leading to accumulation of undigested photoreceptor outer segments and AVL. Clinicians should be aware of this common cause of vitelliform lesions and the poor visual prognosis due to the high risk of atrophy development.

Progression of Pentosan Polysulfate Sodium Maculopathy in a Prospective Cohort.

PURPOSE: To describe the progression of pentosan polysulfate sodium (PPS) maculopathy after drug discontinuation qualitatively and quantitatively using multimodal imaging assessmen. DESIGN: Prospective case series. METHODS: Patients with PPS maculopathy were evaluated after discontinuation of PPS. Near-infrared reflectance (NIR), fundus autofluorescence (FAF), and optical coherence tomography (OCT) were evaluated in all patients at baseline and at the final follow-up visit at least 12 months later. A qualitative and quantitative analysis of the retinal imaging findings was performed. Patterns of disease progression were evaluated. Area of disease involvement on FAF, retinal pigment epithelium (RPE) atrophy on FAF and NIR, and retinal layer thicknesses on OCT were measured at baseline and at the follow-up visit. RESULTS: A total of 26 eyes were included, with a follow-up period ranging from 13 to 30 months. The diseased area measured on FAF showed significant expansion in all eyes from baseline to follow-up despite drug cessation (P = .03) with a median linearized rate of change of 0.42 mm/y. There was significant reduction in the central macular thickness (P = .04), inner nuclear layer thickness (P = .003), outer nuclear layer thickness (P = .02), and subfoveal choroidal thickness (P = .003) at follow-up vs baseline. New areas of RPE atrophy on FAF in the macula developed in 4 eyes while preexisting atrophic lesions increased in size in 5 eyes. CONCLUSION: Eyes with baseline PPS maculopathy all exhibited remarkable progression with qualitative and quantitative multimodal imaging analysis despite drug discontinuation. Disease progression may be attributed to underlying inner choroidal ischemia or RPE impairment.

Vitelliform maculopathy: Diverse etiologies originating from one common pathway.

Vitelliform lesions (VLs) are associated with a wide array of macular disorders but are the result of one common pathway: retinal pigment epithelium (RPE) impairment and phagocytic dysfunction. VLs are defined by the accumulation of yellowish subretinal material. In the era of multimodal advanced retinal imaging, VLs can be further characterized by subretinal hyperreflectivity with optical coherence tomography and hyperautofluorescence with fundus autofluorescence. VLs can be the result of genetic or acquired retinal diseases. In younger patients, VLs usually occur in the setting of Best disease. Additional genetic causes of VL include pattern dystrophy or adult-onset vitelliform macular dystrophy. In older patients, acquired VLs can be associated with a broad spectrum of etiologies, including tractional, paraneoplastic, toxic, and degenerative disorders. The main cause of visual morbidity in eyes with VLs is the onset of macular atrophy and macular neovascularization. Histopathological studies have provided new insights into the location, nature, and lifecycle of the vitelliform material comprised of melanosomes, lipofuscin, melanolipofuscin, and outer segment debris located between the RPE and photoreceptor layer. Impaired phagocytosis by the RPE cells is the unifying pathway leading to VL development. We discuss and summarize the nature, pathogenesis, multimodal imaging characteristics, etiologies, and natural course of vitelliform maculopathies.

Relationship Between Drusen Height and OCT Biomarkers of Atrophy in Non-Neovascular AMD.

Purpose: To determine if increasing drusen height correlates with predictive optical coherence tomography (OCT) biomarkers of atrophy. Methods: Retrospective cross-sectional study that enrolled patients with drusen associated with intermediate AMD. Macular drusen were classified as small, intermediate, large, or very large based on OCT quartile measurement of height. Drusen diameter was also tabulated. The presence and localization of the OCT biomarkers of atrophy were assessed: disruption of the external limiting membrane and ellipsoid zone, intraretinal hyper-reflective foci, RPE disruption, choroidal hypertransmission, and presence of hyporeflective cores. Predictive OCT biomarkers of atrophy were correlated with drusen height. Results: A total of 155 eyes from 104 patients met the inclusion and exclusion criteria. The mean age was 75.7 ± 8.7 years, and patients were predominantly female (74.0%). The mean visual acuity was logMAR 0.2 ± 0.2 (Snellen equivalent 20/32). The average drusen height was 134.6 ± 107.5 µm and the greatest horizontal diameter was 970.7 ± 867.4 µm. Disruption of the external limiting membrane and ellipsoid zone, RPE thickening or thinning, intraretinal hyper-reflective foci, choroidal hypertransmission, and presence of hyporeflective cores (P < 0.05) were more common in eyes with large drusen and very large drusen versus small or intermediate drusen. All biomarkers were positively correlated with drusen height. OCT biomarkers of atrophy were predominantly located at the apex of the drusen. Conclusions: Predictive OCT biomarkers of atrophy, specifically signs of RPE breakdown and disruption, occur more commonly in large or very large drusen, especially in drusen with greater height and separation of the RPE from the underlying choroid.

Pentosan Polysulfate Sodium-Associated Maculopathy: Early Detection Using OCT Angiography and Choriocapillaris Flow Deficit Analysis.

PURPOSE: To compare choriocapillaris flow deficit (CC-FD) analysis using optical coherence tomography angiography (OCTA) in eyes of patients treated with high cumulative dosages of pentosan polysulfate sodium (PPS) but no signs of retinal toxicity versus healthy age-matched controls. DESIGN: Retrospective clinical cohort study. METHODS: Patients treated with PPS for interstitial cystitis with a cumulative dose of > 1000 g underwent multimodal imaging screening to exclude evidence of PPS maculopathy or other retinal findings. All study patients and age-matched healthy controls completed a 3 × 3 mm macular volume scan OCTA using the SOLIX full-range OCT. En face OCTA images at the level of the CC were exported and CC-FDs were computed and compared between groups. RESULTS: Fifteen patients treated with PPS and 15 age-matched controls were included. The mean PPS cumulative dose was 1974 ± 666 g over a mean of 17.6 ± 6.8 treatment years. All patients registered a visual acuity of 20/25 or better and normal fundus autofluorescence (FAF), OCT, multicolor, near-infrared reflectance (NIR), and ultra-widefield fundus color and autofluorescence images. The CC-FD was 32.7 ± 3.6% in the PPS group compared with 28.6 ± 4.3% in the control group (P = .023). CONCLUSIONS: Patients treated with PPS long enough to accumulate dosages > 1000 g showed significant CC flow impairment before the development of macular toxicity signs with OCT, NIR, and FAF compared with age-matched normal controls. Thus, the choroid may be the earliest manifestation of ocular toxicity, predating the development of clinically evident retinal pigment epithelium (RPE) injury. The subsequent RPE disruption may be the result of choriocapillaris impairment or primary PPS toxicity. Assessment of the CC on OCTA may be a useful tool for early detection of toxicity, although further longitudinal studies are required.

Clinical and Morphologic Characteristics of Perivenular Fernlike Leakage on Ultrawide-field Fluorescein Angiography.

PURPOSE: To analyze the spectrum of the perivenular fernlike leakage on ultrawide-field fluorescein angiography (UWFA) and discuss its potential implications in the current understanding of the retinal venous outflow. DESIGN: Retrospective, observational case series. PARTICIPANTS: Eyes presenting with fernlike patterns of dye leakage on UWFA were included in this study. METHODS: Analysis of the clinical characteristics and multimodal imaging findings using UWFA and wide-angle swept-source OCT-angiography (SS-OCTA). MAIN OUTCOME MEASURES: The disease spectrum, anatomic origin, and clinical implications of this fernlike leakage. RESULTS: Multimodal retinal images from 40 eyes of 29 patients with fernlike leakage on UWFA were studied. The underlying etiologies included a wide range of inflammatory disorders, including pars planitis (18 eyes) and central retinal vein occlusion (2 eyes). On UWFA, the fernlike leakage originated from the retinal capillaries and venules directly adjacent to the veins and spared the periarterial zone. This perivenular fernlike leakage involved the far periphery in all cases and progressed more diffusely and centripetally in cases with more severe intraocular inflammation. On wide-angle SS-OCTA, the impairment of deep capillary plexus (DCP) flow signals precisely colocalized with the perivenular fernlike leakages identified on UWFA. CONCLUSIONS: The fernlike leakage on UWFA refers to the distinctive perivenular dye leakage that originates from the retinal capillaries and venules. Multimodal imaging correlation suggests that the predominant impairment is at the level of the DCP. The axial symmetry of the fernlike leakage with the veins and sparing of the periarterial zone may support the dominant venous role of the DCP.

New frontiers of retinal therapeutic intervention: a critical analysis of novel approaches.

A recent wave of pharmacologic and technologic innovations has revolutionized our management of retinal diseases. Many of these advancements have demonstrated efficacy and can increase the quality of life while potentially reducing complications and decreasing the burden of care for patients. Some advances, such as longer-acting anti-vascular endothelial growth factor agents, port delivery systems, gene therapy, and retinal prosthetics have been approved by the US Food and Drug Administration, and are available for clinical use. Countless other therapeutics are in various stages of development, promising a bright future for further improvements in the management of the retinal disease. Herein, we have highlighted several important novel therapies and therapeutic approaches and examine the opportunities and limitations offered by these innovations at the new frontier. KEY MESSAGESNumerous pharmacologic and technologic advancements have been emerging, providing a higher treatment efficacy while decreasing the burden and associated side effects.Anti-vascular endothelial growth factor (anti-VEGF) and its longer-acting agents have dramatically improved visual outcomes and have become a mainstay treatment in various retinal diseases.Gene therapy and retinal prosthesis implantation in the treatment of congenital retinal dystrophy can accomplish the partial restoration of vision and improved daily function in patients with blindness, an unprecedented success in the field of retina.

Henle Fiber Layer Hemorrhage in Macular Telangiectasia Type 2: Is Right Eye Dominance Coincidence or Consequence?

PURPOSE: To summarize all reported cases of Henle fiber layer (HFL) hemorrhage in the absence of subretinal neovascularization (SRNV) in patients with macular telangiectasia type 2 (MacTel2) and to propose a mechanism for the right-sided predominance of this unique presentation. DESIGN: Perspective. METHODS: Collection, review, and analysis of all cases in the literature and in the authors' databases of HFL hemorrhage in MacTel2, including analysis of baseline and follow-up multimodal retinal imaging findings of selected cases. Elucidation of the complex interplay of systemic venous pressure with the deep retinal capillary plexus and hypothesis regarding the right-sided predilection of HFL hemorrhage complicating MacTel2. RESULTS: Ten patients presented with a unilateral, characteristic radial macular hemorrhage within the HFL that affected only the right eye in all cases. Absence of SRNV was confirmed by fluorescein angiography and/or optical coherence tomography angiography. The hemorrhage resolved spontaneously in at least 7 of the 10 eyes. The HFL hemorrhage may plausibly be explained by dysfunction of the deep capillary plexus in MacTel2 combined with an acute rise in central venous pressure, for which the right side may be at increased risk. CONCLUSIONS: HFL hemorrhage can complicate MacTel2 in the absence of SRNV, and the radial pattern of blood affecting only the right eye is remarkable. The right eye predominance may be multifactorial in etiology. Related factors may include the right-sided predilection of MacTel2 and/or increased right-sided dural sinus drainage related to normal anatomical variation.

ASSOCIATION OF CHOROIDAL THICKNESS WITH RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To compare the choroidal thickness before and after pars plana vitrectomy for rhegmatogenous retinal detachment repair. METHODS: A retrospective case series of rhegmatogenous retinal detachment patients presenting between January 2015 and September 2020. Subfoveal choroidal thickness (SFCT) and anatomical success were measured in operated eyes and fellow eyes at presentation, as well as 3 months and 6 months after pars plana vitrectomy for rhegmatogenous retinal detachment repair. RESULTS: A total of 93 patients (males 59%) with a mean age of 61.8 ± 15.2 years were included. Eighty-one patients were anatomically successful (Group 1) and 12 redetached (Group 2). The mean SFCT of the operated eye at presentation was 258.3 ± 82.0 µm in comparison with 257.5 ± 83.7 µm in the fellow eye (P = 0.96). Group 2 presented with thicker SFCT than Group 1 at baseline (309.2 ± 56.2 vs. 250.7 ± 82.8 µm; P = 0.01). Both groups demonstrated thinning trend throughout follow-up. At 6-month follow-up, the mean SFCT was 225.6 ± 75.5 µm (P = 0.05). Fellow-eye SFCT was stable throughout follow-up (257 ± 83.7 at baseline vs. 255 ± 80.2 µm at 6 months). CONCLUSION: Eyes with rhegmatogenous retinal detachment demonstrated thinning in the SFCT after vitrectomy surgery. Eyes with recurrent retinal detachment presented with a thicker choroid at baseline. Thicker SFCT at presentation may play a role in retinal redetachment.

Coincident PAMM and AMN and Insights Into a Common Pathophysiology.

PURPOSE: To analyze imaging characteristics and the clinical course of patients demonstrating coincident lesions of paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) in the same eye. DESIGN: Retrospective, observational case series. METHODS: Lesions from patients presenting with coincident PAMM and AMN in the same eye were evaluated with multimodal imaging including optical coherence tomography (OCT). The association with ocular and systemic findings was also investigated. RESULTS: Fifteen subjects (17 eyes) were included in the study. The mean age was 44.4 ± 15.3 years and the follow-up period ranged from 1 to 32 weeks (mean, 11.9 ± 11.4 weeks). The mean visual acuity was 0.8 ± 0.6 logarithm of minimal angle of resolution (Snellen equivalent 20/126) at baseline and 0.3 ± 0.4 logarithm of minimal angle of resolution (Snellen equivalent 20/40) at the last follow-up. PAMM and AMN lesions occurred in the setting of Purtscher's retinopathy (4 eyes, 3 patients), retinal vein occlusion (7 eyes, 7 patients), central retinal artery occlusion (1 eye, 1 patient), and idiopathic retinal vasculitis (1 eye, 1 patient). In 4 eyes (3 patients), an association with other ocular disorders was not identified as evaluated with multimodal imaging. Of the total cohort, 11 eyes (64.7%) showed extension of the AMN hyperreflective bands in Henle's fiber layer with a Z-shaped morphology on OCT B-scan. CONCLUSIONS: The presence of coincident PAMM and AMN suggests a common pathophysiologic etiology. This may be the result of retinal vein impairment and hypoperfusion at the level of the deep retinal capillary plexus possibly leading to injury to the Müller glia or photoreceptors in Henle's fiber layer.

Advanced OCT Analysis of Biopsy-proven Vitreoretinal Lymphoma.

PURPOSE: Although diagnosing vitreoretinal lymphoma (VRL) can be challenging, early detection is critical for visual prognosis. We analyzed the spectrum of optical coherence tomography (OCT) findings in patients with biopsy-proven VRL and correlate these features with clinical parameters. DESIGN: This retrospective cross-sectional study was a multicenter chart review from 13 retina, uveitis, and ocular oncology clinics worldwide from 2008 to 2019. We included patients with a diagnosis of biopsy-proven VRL imaged with OCT at presentation. Ocular information, systemic information, and multimodal retinal imaging findings were collected and studied. The main outcome measure was the characteristics of VRL on OCT. RESULTS: A total of 182 eyes of 115 patients (63 women, mean age 65 years) were included in this study. The disease was bilateral in 81 patients (70%), and mean baseline visual acuity was 0.2 ± 0.89 logMAR (Snellen equivalent, 20/32). At baseline, 38 patients (33%) presented with isolated ocular involvement, 54 (45%) with associated central nervous system involvement, and 11 (10%) with other systemic lymphomatous involvement; an additional 12 patients (10%) presented with central nervous system and other systemic involvement. On OCT, tumor infiltration was identified in various retinal layers, including lesions in the subretinal pigment epithelium compartment (91% of eyes), the subretinal compartment (43% of eyes), and the intraretinal compartment (7% of eyes). OCT analysis of eyes with VRL identified 3 main regions of retinal infiltration. Subretinal pigment epithelium location, with or without subretinal infiltration, was the most common pattern of involvement and isolated intraretinal infiltration was the least.

PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: Long-Term Visual Acuity May Improve With Higher Injection Index.

PURPOSE: To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. METHODS: Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: <9). RESULTS: Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. CONCLUSION: Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

En Face Optical Coherence Tomography Imaging of Foveal Dots in Eyes With Posterior Vitreous Detachment or Internal Limiting Membrane Peeling.

Purpose: To analyze the morphology of foveal hyperreflective dots (HRD) identified with en face optical coherence tomography (OCT) and evaluate the effects of internal limiting membrane (ILM) peeling and posterior vitreous detachment (PVD) on the number of these lesions. Methods: Retrospective cross-sectional study of patients with OCT angiography and en face OCT. Using en face OCT, superficial HRD lying on the foveal floor were measured and quantitated in eyes with ILM peel and in the fellow nonsurgical eyes. Eyes with foveal PVD were also compared to fellow eyes without foveal PVD. High-magnification en face OCT was also performed to better understand the morphology of HRD in the fovea. Results: Eyes that underwent ILM peel (n = 10) displayed fewer HRD (P = 0.012) compared to control fellow nonoperated eyes. In eyes with foveal PVD, the mean number of HRD was numerically greater, but without statistical significance, compared to the contralateral eye without foveal PVD. High-magnification en face OCT illustrated HRD with irregular shapes and fine cilia-like or dendriform extensions. Average length of HRD was between 15 to 21 µm in all four groups. Conclusions: HRD decreased in eyes with ILM peeling by en face OCT compared with fellow nonoperated eyes and exhibited a glial cell-like morphology and size closely resembling the white dot fovea described previously using scanning electron microscopy. HRD may represent processes of activated retinal glia, possibly Muller cells, that traverse defects in the ILM.

Prevalence of Focal Inner, Middle, and Combined Retinal Thinning in Diabetic Patients and Its Relationship With Systemic and Ocular Parameters.

Purpose: To determine the prevalence of focal inner, middle, and combined inner/middle retinal thinning (FIRT, FMRT, and FCRT, respectively) in different stages of diabetic retinopathy (DR) without diabetic macular edema and to assess the relationship between such findings with ocular and systemic parameters. Methods: This was a cross-sectional, comparative study comprising healthy participants and diabetic patients with different stages of DR. Forty-nine horizontal macular B-scans from the selected eye were obtained using spectral-domain optical coherence tomography (SD-OCT) and analyzed for the presence of FIRT, FMRT, or FCRT and any relationship with systemic and ocular parameters. Focal retinal thinning (FRT) was subjectively defined as any evidence of inner and/or middle retinal thinning. Results: A total of 190 participants (52 healthy participants and 138 diabetic patients) were included. A higher prevalence of FRT was observed in eyes with advanced DR versus healthy eyes and versus diabetic eyes with no DR or mild DR. FIRT and FCRT were significantly greater in eyes with proliferative DR treated with pan-retinal photocoagulation, and FMRT was significantly more common in eyes with severe nonproliferative DR. FRT was significantly more common in patients with coronary artery disease and was positively correlated with diabetes duration, serum creatinine, and glycosylated hemoglobin and negatively correlated with age, estimated glomerular filtration rate, and visual acuity. Conclusions: FRT occurs in all stages of DR and is increasingly prevalent with increasing severity of DR. Translational Relevance: OCT identification of FRT may provide a surrogate biomarker of retinal and systemic disease in diabetic patients.

Pentosan Polysulfate Maculopathy: Prevalence, Spectrum of Disease, and Choroidal Imaging Analysis Based on Prospective Screening.

PURPOSE: To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis. DESIGN: Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed. RESULTS: The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo- and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5±5.5 years, 433.9±137.6 mg, 3,103.1±1,402.2 g) compared with the unaffected cohort (7.1±6.6 years, 291.6±177.6 mg, 768.4±754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group. CONCLUSIONS: This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity.

Identification and Characterization of Epivascular Glia Using En Face Optical Coherence Tomography.

PURPOSE: The purpose of this study was to describe the clinical features of epivascular glia (EVG) using en face optical coherence tomography (OCT). DESIGN: Retrospective cross-sectional study. METHODS: Single-institution en face OCT images were reviewed. Eyes displaying EVG were captured with manual internal limiting membrane (ILM) segmentation and analyzed with customized segmentation . A random age- and sex-matched control group was selected to determine relative epiretinal membrane (ERM) prevalence. RESULTS: Characteristic hyper-reflective ILM plaques with dendrite-like radiations were identified using en face OCT and displayed vascular predilection. A total of 161 eyes with EVG (the EVG group) and 2,315 eyes without EVG (control group) were identified from a total cohort of 1,298 patients (or 2,476 eyes). The prevalence of EVG was 161 of 2,476 eyes (6.5%) and 119 of 1,298 patients (9.2%) in the cohort. Mean age was 79.3 ± 10.7 years old in the EVG group and 55.9 ± 24.6 years old in the control group (P <.001). An advanced posterior vitreous detachment (PVD) stage was more common in the EVG group (grade 3: 41.7%; grade 4: 48.6%) than in the control group (grade 3: 18.5%; grade 4: 26.9%; P <.001). Contractile ERM was present in 71 of 161 eyes (44.1%) with EVG compared to 30 of 161 eyes (18.6%) in a random age- and sex-matched control cohort without EVG (P <.001). CONCLUSIONS: EVG previously described with histopathology and scanning electron microscopy can be identified using en face OCT. In this study, these lesions were associated with older age, pseudophakia, and advanced PVD, supporting the role of Müller cell activation through ILM breaks triggered by PVD, a pathogenic mechanism proposed by previous studies.