Postoperative magnetic resonance imaging of the inferior oblique muscle.

No previous imaging study has described the appearance of the inferior oblique muscle after surgery. It is unknown whether findings signifying prior myectomy or recession are recognizable on magnetic resonance (MR) imaging and how they might differ for the two procedures. After myectomy via a temporal approach, the cauterized muscle stump retracts into the medial orbit. How far it retracts and whether it reattaches to the globe remains unclear. To address these issues, orbital MR images were reviewed in 5 patients who had previously undergone inferior oblique myectomy or recession. In each case, the operated muscle exhibited subtle but telltale features, when compared with the normal, fellow inferior oblique. After myectomy, the inferior oblique still terminated lateral to the inferior rectus muscle and appeared closely apposed to the globe, although not necessarily attached to the sclera.

Individual and Systems-Based Risk Factors for Diabetic Vitrectomy in an Urban Safety-Net Hospital.

OBJECTIVE: To identify individual and systems-focused risk factors for pars plana vitrectomy among patients with proliferative diabetic retinopathy (PDR) in a diverse, urban, safety-net hospital setting. DESIGN: Single-center, retrospective, observational, case-control study at Zuckerberg San Francisco General Hospital and Trauma Center between 2017 and 2022. SUBJECTS: Two hundred twenty-two patients with PDR over a 5-year span (2017-2022), consisting of 111 cases who underwent vitrectomy for vision-threatening complications (tractional retinal detachment, nonclearing vitreous hemorrhage, and neovascular glaucoma) and 111 controls with PDR with no history of vitrectomy or vision-threatening complications. Controls were matched 1:1 through incidence density sampling. METHODS: Medical records were reviewed from time of entry into hospital system to vitrectomy date (or date-matched clinic visit for controls). Individual-focused exposures included age, gender, ethnicity, language, homelessness, incarceration, smoking status, area deprivation index, insurance status, baseline retinopathy stage, baseline visual acuity, baseline hemoglobin A1c, panretinal photocoagulation status, and cumulative anti-VEGF treatments. System-focused exposures included external department involvement, referral route, time within hospital and ophthalmology systems, interval between screening and ophthalmology appointment, interval between conversion to proliferative disease and panretinal photocoagulation or first treatment, and loss-to-follow-up in intervals of active proliferative disease. MAIN OUTCOME MEASURES: Odds ratios (ORs) for each exposure on vision-threatening diabetic complications requiring vitrectomy. RESULTS: The absence of panretinal photocoagulation was the primary significant individual-focused risk factor for vitrectomy in the multivariable analysis (OR, 4.78; P = 0.011). Systems-focused risk factors included longer interval between PDR diagnosis and initial treatment (weeks; OR, 1.06; P = 0.024) and greater cumulative duration of loss-to-follow-up during intervals of active PDR (months; OR, 1.10; P = 0.002). Greater duration in the ophthalmology system was the primary systems-focused protective factor against vitrectomy (years; OR, 0.75; P = 0.035). CONCLUSIONS: Largely modifiable variables modulate risk of complications requiring diabetic vitrectomy. Each additional month of loss-to-follow-up for patients with active proliferative disease increased odds of vitrectomy by 10%. Optimizing modifiable factors to promote earlier treatment and maintain critical follow-up in proliferative disease may reduce vision-threatening complications requiring vitrectomy in a safety-net hospital setting. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cone Structure and Function in RPGR- and USH2A-Associated Retinal Degeneration.

PURPOSE: To compare cone structure and function between RPGR- and USH2A-associated retinal degeneration. DESIGN: Retrospective, observational, cross-sectional study. METHODS: This multicenter study included 13 eyes (9 participants) with RPGR-related X-linked retinitis pigmentosa (RPGR), 15 eyes (10 participants) with USH2A-related Usher syndrome type 2 (USH2), 16 eyes (9 participants) with USH2A-related autosomal recessive retinitis pigmentosa (ARRP), and 7 normal eyes (6 participants). Structural measures included cone spacing and density from adaptive optics scanning laser ophthalmoscopy and photoreceptor inner segment (IS), outer segment (OS), and outer nuclear layer (ONL) thickness from optical coherence tomography (OCT) images. OCT angiography images were used to study choriocapillaris flow deficit percent (CCFD). Cone function was assessed by fundus-guided microperimetry. Measures were compared at designated regions using analysis of variance with pairwise comparisons among disease groups, adjusted for disease duration and eccentricity. RESULTS: OCT segmentation revealed shorter OS and IS, with reduced ONL thickness in RPGR compared to normal (OS: P < .001, IS: P = .001, ONL: P = .005), USH2 (OS: P = .01, IS: P = .03, ONL: P = .03), or ARRP (OS: P = .001, ONL: P = .03). Increased cone spacing was observed in both RPGR (P = .03) and USH2 compared with normal (P = .048). The mean CCFD in RPGR was greater than in USH2 (P = .02). Microperimetry demonstrated below-normal regional sensitivity in RPGR (P = .004), USH2 (P = .02), and ARRP (P = .009), without significant intergroup differences. CONCLUSIONS: Outer retinal structure and choriocapillaris perfusion were more abnormal in RPGR- than USH2A-related retinal degenerations, whereas there were no significant differences in below-normal regional sensitivity between each rod-cone degeneration associated with variants in these 2 genes expressed at the photoreceptor-connecting cilium.

Topographic Relationship between Telangiectasia and Cone Mosaic Disruption in Macular Telangiectasia Type 2.

In this cross-sectional observational study, we investigated the relationship between photoreceptor layer disruption and telangiectasia in patients diagnosed with early stage macular telangiectasia type 2 (MacTel). A total of 31 eyes (17 patients) with MacTel were imaged with adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography angiography (OCTA). Confocal AOSLO was used to visualize dark regions of nonwaveguiding outer segments, which we refer to as "photoreceptor lesions". En-face OCTA images of the deep capillary plexus (DCP) were used in conjunction with confocal AOSLO to evaluate the topographic relationship between areas of capillary telangiectasias and photoreceptor lesions. Among seven eyes with early stage MacTel (stage 0-2 based on OCT), we identified ten photoreceptor lesions, all of which were located within parafoveal quadrants containing DCP telangiectasia on OCTA. Seven of the lesions corresponded to the intact ellipsoid zone on spectral-domain OCT (SD-OCT), and three of these also corresponded to the intact interdigitation zone. This work demonstrates a topographic relationship between AOSLO photoreceptor lesions and DCP telangiectasias, and it also suggests that these lesions with normal SD-OCT appearance may represent areas of photoreceptors at risk for dysfunction. Thus, confocal AOSLO may have a meaningful role in detecting early photoreceptor abnormalities in eyes with MacTel.

Perivenular Capillary Loss: An Early, Quantifiable Change in Macular Telangiectasia Type 2.

Purpose: To evaluate differences in parafoveal vascular density surrounding arterioles and venules in type 2 macular telangiectasia (MacTel). Methods: Thirty-seven eyes (20 subjects) diagnosed with MacTel and 16 healthy eyes (10 subjects) were imaged with optical coherence tomography angiography between March 2016 and June 2019 in this single-center, observational, cross-sectional study. Arterioles and venules were manually identified, and perivascular density was generated using a custom MATLAB code. The primary outcome measure was the ratio of periarteriolar to perivenular vascular density (arteriovenous [A/V] capillary ratio) in the superficial and deep capillary plexuses across MacTel stages. The main secondary outcome measures were overall parafoveal vascular density (VD), periarteriolar VD, and perivenular VD. Results: In the superficial capillary plexus (SCP), the A/V capillary ratio was significantly higher in MacTel subjects than controls (0.914 vs. 0.892; P = 0.0044). The greatest differences occurred between controls and nonproliferative MacTel subjects without optical coherence tomography evidence of disease (P = 0.0055). A/V capillary ratios progressed in a nonlinear fashion with MacTel severity, increasing from nonproliferative disease (0.912) to intraretinal proliferative disease (0.931), then decreasing in subretinal proliferative disease (0.905). Parafoveal VD in the SCP was lower in MacTel subjects than controls only in subretinal proliferative disease (P = 0.0130). Conclusions: The A/V capillary ratio of the SCP is a quantifiable metric of vascular pathology in MacTel that occurs earlier than decline in parafoveal VD. Elevated A/V capillary ratios in MacTel are consistent with an early, disproportionately perivenular disruption in the SCP. Translational Relevance: Findings inform MacTel pathogenesis through revealing early perivenular capillary loss and offer a new quantitative metric for earliest stage MacTel.

Overlap between telangiectasia and photoreceptor loss increases with progression of macular telangiectasia type 2.

OBJECTIVES: To examine the topographical correlation between ellipsoid zone loss and telangiectasia in the deep capillary plexus in patients with macular telangiectasia type 2 (MacTel). METHODS: 38 eyes (20 subjects) diagnosed with MacTel were imaged with OCTA between March 2016 and June 2019 in this single center, cross-sectional observational study. The en face OCTA and OCT were evaluated for areas of deep capillary plexus telangiectasia and ellipsoid zone loss, respectively, and their outlines were superimposed to study their overlap (mm2). The primary outcome was percentage of overlap and its relationship to MacTel stage. Secondary outcomes included the relationship between neovascularization and hyperreflective foci as well as correlations between ellipsoid zone loss, deep capillary plexus telangiectasia and visual acuity. RESULTS: In nonproliferative MacTel stage, ellipsoid zone loss was localized to margins of telangiectatic areas (mean overlap = 15.2%). In proliferative stages, ellipsoid zone loss showed a higher degree of overlap with telangiectatic areas (mean overlap = 62.8%). Overlap increased with advancing MacTel stages, with an overall average of 45.3%. Overlap correlated highly with ellipsoid zone loss (r = 0.831; p<0.0001). Telangiectasia was present in all 38 eyes (range: 0.08mm2-0.99mm2), while ellipsoid zone loss was absent in 6 (range: 0.00-3.32mm2). Visual acuity correlated most strongly with ellipsoid zone loss (r = 0.569; p = 0.0002), followed by overlap (r = 0.544; p = 0.0004), and finally, telangiectasia (r = 0.404; p<0.0118). Presence of hyperreflective foci on OCT correlated with the presence and intraretinal location of neovascularization. CONCLUSIONS: Ellipsoid zone loss occurs at the margins of deep capillary plexus telangiectasia in nonproliferative MacTel, with progressively increasing overlap as MacTel advances, peaking in proliferative disease. Deep capillary plexus telangiectasia and its overlap with ellipsoid zone loss are two promising markers of nonproliferative MacTel, while hyper-reflective foci are markers for proliferative MacTel.

Optimizing methods to quantify intramuscular fat in rotator cuff tears with normalization.

OBJECTIVE: To determine which normalization method may best account for confounding individual factors, such as age or BMI, when quantifying fat infiltration on MRI in patients with rotator cuff tears, the effects of normalization using three different muscles (teres major; triceps brachii; teres minor) were compared. METHODS: Thirty-seven consecutive patients diagnosed with rotator cuff pathology were included. MRI fat-water sequences were used to quantify rotator cuff intramuscular fat (%fat). Three reference muscles (teres major, triceps, teres minor) were used to derive normalized %fat. Relationships between intramuscular %fat and tear size, age, and BMI in each rotator cuff muscle, before and after normalization, were compared with Fisher transformations (α = 0.05). RESULTS: Normalization with teres major ameliorated confounding relationships of age and BMI on rotator cuff %fat. In contrast, normalization with triceps maintained the confounding relationships between %fat and age in supraspinatus (p = 0.03) and infraspinatus/teres minor (p = 0.028). Normalization with teres minor maintained the confounding relationship between %fat and BMI in subscapularis (p = 0.039). Normalization with teres major best-maintained relationships between tear size and infraspinatus/teres minor %fat (p = 0.021). In contrast, normalization with triceps or teres minor eliminated all significant relationships with tear size. CONCLUSIONS: Results of this pilot study suggest normalization to teres major using MRI-based %fat quantification methods can effectively control for individual factors, such as BMI or age, and may have utility in evaluating and monitoring rotator cuff fat infiltration attributed specifically to a tendon tear.

Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis.

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1ß levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease.