Faculty Bibliography

En face optical coherence tomography (OCT) is a practical and informative imaging modality to noninvasively visualize distinct retinal and choroidal layers by providing coronal images using boundary-specific segmentation. Ongoing research with this method is generating breakthroughs in the illustration of new perspectives of retinal disease. The clinical value of en face OCT as an advanced retinal imaging tool is growing steadily and it has unveiled many new insights into the pathoanatomy of retinal disorders. Moreover, this modality can capture various en face OCT biomarkers that correspond to different cell or tissue subtypes, which were previously only identified through histological or electron microscopy methods, underscoring the significance of this technique in providing valuable pathoanatomical information. In this comprehensive review, we will systematically summarize the en face OCT findings across a broad spectrum of retinal diseases, including disorders of the vitreoretinal interface and retinal vascular system (e.g. paracentral acute middle maculopathy or PAMM and diabetic retinopathy), in addition to the en face OCT features of other conditions such as age-related macular degeneration, pachychoroid disease spectrum, myopic degeneration, uveitis and inflammatory disorders, inherited retinal dystrophies, and drug toxicity. We will discuss and highlight the unique clinical and pathoanatomical findings uncovered with en face OCT of each these diseases mentioned above.

PURPOSE/UNASSIGNED:To advance metabolic imaging of the high-risk macula lutea by quantifying the topography of macular pigment optical density (MPOD), measured with two-wavelength autofluorescence (2WAF), and quantitative (short-wavelength) autofluorescence (qAF) intensity, which share the same signal source and cross-retinal light path, in aging, early (e), and intermediate (i) age-related macular degeneration (AMD). METHODS/UNASSIGNED:2WAF and qAF images of 384 pseudophakic eyes of 230 persons (mean age, 74.2 ± 5.7 years; 145 female) from ALSTAR2 (AREDS 9-step classification: 170, normal; 118, eAMD; 96 iAMD) were shown as maps (intensity, z-score) and meridian plots. Correlations were determined in Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. RESULTS/UNASSIGNED:MPOD was higher in the central subfield (P < 0.01) in iAMD compared to eAMD and normal eyes, and qAF was lower in the central subfield and inner ring (both P < 0.01) in AMD compared to normal eyes. MPOD differed along horizontal versus vertical meridians, depending on disease stage. Pixel-level z-score maps and meridian plots showed distinct annuli of alternating levels of MPOD anchored on the foveal center, unrelated to qAF. Across the central subfield, high 2WAF was associated with low qAF in all disease stages (r = -0.47, r = -0.47, r = -0.42; all P < 0.001). In the inner ring, correlations were significant for normal and eAMD only (r = -0.31, P = 0.004 and r = -0.22, P ≤ 0.001, respectively). CONCLUSIONS/UNASSIGNED:New analytics support previously reported higher MPOD in AMD compared to normal eyes, especially central subfield and inner ring. MPOD and qAF differ by disease-stage-related topography and correlations, supporting independent use in metabolic imaging of the macula lutea.

PURPOSE/UNASSIGNED:To assess corneal resistance to enzymatic digestion after rose bengal (RB)/green light and RB/green light followed by riboflavin (RF)/ultraviolet A (UV-A) cross-linking (CXL), with or without oxygen. METHODS/UNASSIGNED:Ex vivo porcine corneal buttons (n = 144) underwent CXL with RB/green or RB/green-RF/UV-A under atmospheric 21% oxygen conditions or in a nitrogen chamber with 0.1% oxygen (hypoxic conditions) to test 10- and 15-J/cm2 fluences. After CXL, corneas were digested with 0.3% collagenase A, and mean digestion times (MDTs) were recorded. RESULTS/UNASSIGNED:For the non-irradiated control group, the MDT was 19.75 ± 1.34 hours. Under atmospheric oxygen conditions, RB/green CXL yielded MDTs of 33.69 ± 1.4 and 34.38 ± 1.31 hours with fluences of 10 and 15 J/cm2, respectively. RB/green + RF/UV-A showed MDTs of 39.56 ± 1.93 and 51.94 ± 4.2 hours for combined fluences of 10 + 10 J/cm2 and 15 + 15 J/cm2, respectively. Hypoxic RB/green MDTs were 33.88 ± 1.02 and 34.06 ± 1.57 hours, and RB/green + RF/UV-A MDTs were 39.62 ± 2.5 and 50.35 ± 1.59 hours for the same respective fluences. No significant differences were observed between the control groups and corresponding intervention groups (all P > 0.05). CONCLUSIONS/UNASSIGNED:CXL via RB/green and RB/green-RF/UV-A significantly enhanced corneal collagenase digestion resistance, irrespective of oxygen presence. These findings could help optimize infectious keratitis therapy CXL protocols. TRANSLATIONAL RELEVANCE/UNASSIGNED:Our findings aid the understanding of the molecular mechanisms underlying the therapeutic effect of CXL and may contribute to refining accelerated PACK-CXL protocols and other CXL treatment strategies.

PURPOSE/OBJECTIVE:We describe a case of bilateral, multiple, branch retinal artery occlusions (BRAO) associated with carotid webs. METHODS:A thorough chart review was conducted for the patient. Relevant literature was systematically reviewed. RESULTS:Eight cases of fibromuscular dysplasia (FMD) associated with retinal artery occlusions have been reported. Two additional cases of FMD with other ocular involvement have been described. No cases of carotid webs associated with retinal artery occlusions were found. CONCLUSION/CONCLUSIONS:Carotid webs, an uncommon variant of FMD, are a recognized causative etiology of arterial, ischemic stroke. The case described here of bilateral, multifocal BRAOs represents a unique manifestation of this variant of FMD. This diagnosis should be considered in the setting of an otherwise unrevealing BRAO workup, as recognition of this association may be sight and life-saving.

PURPOSE:Due to the slowly progressing nature of age-related macular degeneration (AMD) and critical differences in ocular anatomy between humans and animals, it has been difficult to model disease progression, hampering the development of novel therapeutics aimed at impacting drusen biogenesis. To determine whether "drusen-in-a-dish" model systems are of utility in screening potential therapeutics aimed at early-intermediate dry AMD, we developed a detailed characterization of the protein, glycoprotein, and lipid composition of sub-retinal pigment epithelium (RPE) deposits grown by monolayers of ex vivo porcine RPE with human drusen in AMD globes. METHODS:Immunohistochemistry and imaging mass spectrometry (IMS) were performed on 20-week aged monolayers of porcine RPE and human donor globes recovered from an 81-year-old non-transplant donor with confirmed diagnosis of bilateral dry AMD. The presence of major protein, glycoprotein, and lipid species was compared between porcine sub-RPE deposits and human drusen with reference to macular/peripheral eccentricity. RESULTS:The protein and glycoprotein composition of porcine sub-RPE deposits closely mimics human drusen identified in donor globes with dry AMD, including the presence of major complement components (C9, CFH, CHI), apolipoproteins (ApoE, ApoJ), extracellular matrix proteins (vitronectin, collagen VI), and calcification (hydroxyapatite). Sub-RPE deposits were additionally rich in long-chain ceramide species (Cer, CerPE, PI), which have only recently been described in human drusen. CONCLUSIONS:Due to their compositional similarity to human drusen, ex vivo "drusen-in-a-dish" systems represent a potentially robust and cost-effective model for both studying the pathobiology of drusen biogenesis and screening novel therapeutics aimed at limiting drusen formation.

PURPOSE/OBJECTIVE:To investigate the light transmission (LT) of UV-A and green light through infected corneas saturated with riboflavin or rose bengal in an ex vivo porcine model for infectious keratitis. SETTING/METHODS:University of Zurich and EMPA. DESIGN/METHODS:Laboratory study. METHODS:Ex vivo porcine eyes (n=162) were divided into three groups: control eyes, eyes infected with Staphylococcus aureus, and eyes infected with Pseudomonas aeruginosa. Corneas remained either uninfected, or were infected with S. aureus, and P. aeruginosa, respectively, and were either left untreated, or were instilled with 0.1% riboflavin or 0.1% rose bengal. Corneal buttons were prepared, and corneal LT was measured at 365 nm and 522 nm using a spectrophotometer. LTs were calculated and compared. Transmission electron microscopy (TEM) was used to visualize structural damage and bacteria within infected corneas. RESULTS:Riboflavin-saturated corneas infected by S. aureus or P. aeruginosa (LT = 0.77% [0.41-1.87] and 0.81% [0.23, 1.46]) exhibited 3.18-fold and 3.02-fold lower LTs than uninfected corneas (LT = 2.45% [2.15, 5.89]) (both p-values < 0.001). No LT difference was found between rose bengal-saturated corneas infected by S. aureus or P. aeruginosa and uninfected corneas (all LTs = 0.01% [0.01-0.01]; both p-values = 0.08). TEM showed bacteria on corneal stroma borders and occasionally inside the stroma. CONCLUSION/CONCLUSIONS:Our results indicate that the amount of light arriving at the corneal endothelium is substantially reduced in infected corneas. The total fluence of clinical PACK-CXL protocols can be safely increased substantially while maintaining a low risk of corneal endothelial damage.

PURPOSE/OBJECTIVE:To describe novel findings seen on optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) in a young male patient presenting with bilateral topiramate-induced choroidal effusion. METHODS:Retrospective case report. A comprehensive ophthalmic examination was conducted and multimodal imaging techniques, including B-scan ultrasound, OCT, OCTA, and ICGA were analyzed. RESULTS:A male in his 30s presented with a myopic shift due to bilateral choroidal effusion induced by a medication containing topiramate prescribed for weight loss. ICGA showed multiple hypofluorescent spots within the choroid corresponding to areas of reduced OCTA flow signal in both the inner and deeper en face choroidal slabs. Symptoms and abnormal imaging findings resolved within five days of discontinuing the medication. CONCLUSION/CONCLUSIONS:Findings observed with OCTA and ICGA together suggest multifocal reversible areas of reduced choroidal vascular flow occurring in a topiramate-induced choroidal effusion. We propose that this transient hypoperfusion is due to compression from deeper choroidal vessels with a congested choroid.

PURPOSE/OBJECTIVE:The authors describe a case of Indeterminate cell histiocytosis, a rare disease of histiocytic proliferation on the spectrum of Langerhans cell histiocytosis. METHODS:Data were collected through retrospective chart review. RESULTS:The authors present a novel case of congenital Indeterminate cell histiocytosis with multisystem disease, including significant pan-ocular involvement. The neonate was successfully treated with the BRAF-kinase inhibitor dabrafenib, local anti-VEGF, and corticosteroid. CONCLUSIONS:The present case expands on the current ocular presentations of Indeterminate cell histiocytosis.

PURPOSE/OBJECTIVE:To assess 5-years trends in the rate of immediate sequential bilateral cataract surgery (ISBCS) and surgeon characteristics associated with performing ISBCS. SETTING/METHODS:100% Medicare Fee-for-service beneficiaries from 2018-2022. DESIGN/METHODS:Cross-sectional study. METHODS:ISBCS cases were identified among patients aged ≥ 65 years undergoing bilaterally performed cataract surgery (BPCS). Cochrane Armitage trend test was used to assess patient and surgeon characteristics over time. Multivariable logistic regression was used to evaluate surgeon characteristics associated with performing ISBCS. RESULTS:Among 1,190,169 BPCS, 3,954 (0.33%) were ISBCS. Quarterly ISBCS rate increased from 2.12 to 5.5 per 1,000 BPCS (p<0.001). Among 10,290 surgeons, 1,119 (10.87%) performed ISBCS on some patients. Proportion of surgeons performing ISBCS per 1,000 cataract surgeons increased from 15.63 during the first quarter of 2018 to 26.55 during the last quarter of 2022 (p<0.001). Among the ISBCS surgeons, the proportion of ISBCS cases per 1,000 BPCS doubled from 17.20 in 2018 to 35.50 in 2022 (p<0.001). On multivariable analysis, surgeons in the highest surgical volume quartile (OR: 1.21; 95% CI: 1.01-1.45; Ref: lowest quartile), recent graduates (0-10 years OR: 2.43, 95% CI: 1.87-3.15; Ref: ≥ 31 years) and surgeons in West (OR: 2.408, 95% CI: 2.052-2.826; Ref: South) had higher odds of performing ISBCS. CONCLUSIONS:There was an increased rate of ISBCS possibly suggesting greater interest among patients and surgeons. Although the overall ISBCS rate remained low, the number of surgeons performing ISBCS increased. Higher volume surgeons, recent graduates, and those practicing in the West were more likely to perform ISBCS.

PURPOSE/OBJECTIVE:To evaluate the outcomes of patients treated with corneal allogeneic intrastromal ring segments cut with femtosecond laser (Femto-CAIRS) without concomitant corneal crosslinking. METHODS:Patients with keratoconus treated with Femto-CAIRS at the American University of Beirut Medical Center were included (May 2022-January 2023). A proprietary software program was developed on the femtosecond laser to cut allogeneic segments. Visual, refractive, tomographic, aberrometric, and epithelial data by anterior segment optical coherence tomography were measured at baseline and 1, 3, 6, and 12 months postoperatively. RESULTS:20 eyes of 15 patients were included and followed up for 12 months. The manifest refraction spherical equivalent and cylinder improved from -6.79 ± 4.9 diopter (D) and -4.25 ± 1.8 D to -1.88 ± 2.9 D (P < 0.001) and -2.64 ± 1.4 D (P = 0.01) 12 months postoperatively, respectively. 75% of eyes gained 3 or more corrected distance visual acuity lines, most of which (65%) gained 4 lines or more 12 months postoperatively. The maximum keratometry and vertical coma decreased by 5.2 D (P < 0.001) and 1 μm (P = 0.001), respectively, 3 months postoperatively and remained stable until 12 months. The largest anterior stromal elevation over the central 5-mm diameter decreased from 36.0 ± 18.2 μm preoperatively to 19.9 ± 9.25 μm at 1 week postoperatively (P < 0.001) and remained relatively stable. Epithelial thickness over the cone increased relative to baseline starting 1 month postoperatively and becoming stable after 6 months while the mean epithelial thickness central to the ring peaked at 1 month after which it decreased to reach a plateau at 6 months. CONCLUSIONS:The Femto-CAIRS procedure improves visual and tomographic parameters and allows repeatable and safe results with the possibility of customization for individualized management.