Optical coherence tomography Angio-B mode for early detection of myopic choroidal neovascularization and treatment with Bevacizumab.

Purpose: The purpose of this case report is to outline the management of a 41-year-old female with pathological myopia and type II choroidal neovascularization (CNV) diagnosed by optical coherence tomography angiography (OCT-A) angio-B mode. Observations: The early detection of CNV with OCT-A angio-B mode and treatment with intra-vitreous injections of Bevacizumab contributed to the amelioration of her vision to 20/20, a better visual acuity than she had prior to treatment. Conclusions and importance: This case report suggests that an OCT-A scan may reveal the initial formation of abnormal vasculature before pathological changes are evident in structural OCT, allowing for prompt treatment and resolution in patients with myopic CNV.

Best Disease: Global Mutations Review, Genotype-Phenotype Correlation, and Prevalence Analysis in the Israeli Population.

Purpose: To review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population. Methods: Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources. Results: A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein. Conclusions: This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.

A Novel Device for Suprachoroidal Drug Delivery to Retina: Evaluation in Nonhuman Primates.

Purpose: Evaluation of distribution and tolerance of suprachoroidal injection of indocyanine green (ICG) in nonhuman primates (NHPs) using a novel suprachoroidal (SC) delivery technology. Methods: Three live and three euthanized African green monkeys were injected with 150 or 200 µL ICG/eye into the SC space of both eyes, 2.5 mm posterior to the limbus in the inferior quadrant, utilizing a novel SC injector. Eyes were analyzed by imaging of scleral flatmounts. Live animals were observed for 24 hours for general health. Ophthalmic evaluation included slit-lamp biomicroscopy, tonometry, fundus imaging, confocal laser ophthalmoscopy, and spectral-domain optical coherence tomography (SD-OCT) before and at 10 minutes and 1, 3, and 24 hours post-injection. Results: SC dosing was successfully performed in all eyes. Infrared fundus imaging demonstrated ICG distribution throughout the posterior segment, reaching the macula within 24 hours post-injection. No inflammation, intravitreal penetration, SC blebs, retinal detachment, or hemorrhages were detected. No significant changes were observed in retinal thickness by SD-OCT (P = 0.267, ANOVA). A mild, statistically insignificant elevation in intraocular pressure was observed within 10 minutes post-injection (mean ± standard error: 7.28 ± 5.09 mmHg; P = 0.061) and was spontaneously resolved within the first hour after dosing. Conclusions: Suprachoroidal injection of 150 to 200 µL ICG dye was successfully performed and well tolerated in NHP eyes, with rapid distribution into the macular region and throughout the posterior pole. Translational Relevance: This novel SC drug delivery system may potentially provide safe and effective delivery of therapeutics to the posterior pole region in humans.

PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially modulated by inhibiting the thrombin cellular protease-activated receptor 1 (PAR1). Our aim was to study whether coagulation pathway modulation affects DE. Diabetic C57BL/6 mice were treated with PARIN5, a novel PAR1 modulator. Behavioral changes in the open field and novel object recognition tests, serum neurofilament (NfL) levels and thrombin activity in central and peripheral nervous system tissue (CNS and PNS, respectively), brain mRNA expression of tumor necrosis factor α (TNF-α), Factor X (FX), prothrombin, and PAR1 were assessed. Subtle behavioral changes were detected in diabetic mice. These were accompanied by an increase in serum NfL, an increase in central and peripheral neural tissue thrombin activity, and TNF-α, FX, and prothrombin brain intrinsic mRNA expression. Systemic treatment with PARIN5 prevented the appearance of behavioral changes, normalized serum NfL and prevented the increase in peripheral but not central thrombin activity. PARIN5 treatment prevented the elevation of both TNF-α and FX but significantly elevated prothrombin expression. PARIN5 treatment prevents behavioral and neural damage in the DE model, suggesting it for future clinical research.

Functional Carbon Quantum Dots for Ocular Imaging and Therapeutic Applications.

Carbon quantum dots (CDs) are a class of emerging carbonaceous nanomaterials that have received considerable attention due to their excellent fluorescent properties, extremely small size, ability to penetrate cells and tissues, ease of synthesis, surface modification, low cytotoxicity, and superior water dispersion. In light of these properties, CDs are extensively investigated as candidates for bioimaging probes, efficient drug carriers, and disease diagnostics. Functionalized CDs represent a promising therapeutic candidate for ocular diseases. Here, this work reviews the potential use of functionalized CDs in the diagnosis and treatment of eye-related diseases, including the treatment of macular and anterior segment diseases, as well as targeting Aß amyloids in the retina.

Machine learning for comprehensive prediction of high risk for Alzheimer's disease based on chromatic pupilloperimetry.

Currently there are no reliable biomarkers for early detection of Alzheimer's disease (AD) at the preclinical stage. This study assessed the pupil light reflex (PLR) for focal red and blue light stimuli in central and peripheral retina in 125 cognitively normal middle age subjects (45-71 years old) at high risk for AD due to a family history of the disease (FH+), and 61 age-similar subjects with no family history of AD (FH-) using Chromatic Pupilloperimetry coupled with Machine Learning (ML). All subjects had normal ophthalmic assessment, and normal retinal and optic nerve thickness by optical coherence tomography. No significant differences were observed between groups in cognitive function and volumetric brain MRI. Chromatic pupilloperimetry-based ML models were highly discriminative in differentiating subjects with and without AD family history, using transient PLR for focal red (primarily cone-mediated), and dim blue (primarily rod-mediated) light stimuli. Features associated with transient pupil response latency (PRL) achieved Area Under the Curve Receiver Operating Characteristic (AUC-ROC) of 0.90 ± 0.051 (left-eye) and 0.87 ± 0.048 (right-eye). Parameters associated with the contraction arm of the rod and cone-mediated PLR were more discriminative compared to parameters associated with the relaxation arm and melanopsin-mediated PLR. Significantly shorter PRL for dim blue light was measured in the FH+ group in two test targets in the temporal visual field in right eye that had highest relative weight in the ML algorithm (mean ± standard error, SE 0.449 s ± 0.007 s vs. 0.478 s ± 0.010 s, p = 0.038). Taken together our study suggests that subtle focal changes in pupil contraction latency may be detected in subjects at high risk to develop AD, decades before the onset of AD clinical symptoms. The dendrites of melanopsin containing retinal ganglion cells may be affected very early at the preclinical stages of AD.

Thicker macula in asymptomatic APOE Ɛ4 middle-aged adults at high AD risk.

INTRODUCTION: We compared retinal layers' thickness between apolipoprotein E (APOE) Ɛ4 carriers and non-carriers in a cohort of cognitively normal middle-aged adults enriched for Alzheimer's disease (AD) risk. METHODS: Participants (N = 245) underwent spectral domain optical coherence tomography. Multivariate analyses of covariance adjusting for age, sex, education, and best corrected vision acuity was used to compare retinal thickness between APOE groups. RESULTS: Participants' mean age was 59.60 (standard deviation = 6.42) with 66.4% women and 32.2% APOE Ɛ4 carriers. Greater macular full thickness was observed in APOE Ɛ4 carriers compared to non-carriers (P = .017), reaching statistical significance for the inner and outer nasal (P = .009 and P = .005, respectively), inner superior (P = .041), and inner and outer inferior (P = .013 and P = .033, respectively) sectors. The differences between APOE groups were mainly driven by the ganglion cell layer (P < .05) and the inner plexiform layer (P < .05). DISCUSSION: A thicker macula is observed already in midlife asymptomatic APOE Ɛ4 carriers at high AD risk.

Intrinsic Expression of Coagulation Factors and Protease Activated Receptor 1 (PAR1) in Photoreceptors and Inner Retinal Layers.

The aim of this study was to characterize the distribution of the thrombin receptor, protease activated receptor 1 (PAR1), in the neuroretina. Neuroretina samples of wild-type C57BL/6J and PAR1-/- mice were processed for indirect immunofluorescence and Western blot analysis. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to determine mRNA expression of coagulation Factor X (FX), prothrombin (PT), and PAR1 in the isolated neuroretina. Thrombin activity following KCl depolarization was assessed in mouse neuroretinas ex vivo. PAR1 staining was observed in the retinal ganglion cells, inner nuclear layer cells, and photoreceptors in mouse retinal cross sections by indirect immunofluorescence. PAR1 co-localized with rhodopsin in rod outer segments but was not expressed in cone outer segments. Western blot analysis confirmed PAR1 expression in the neuroretina. Factor X, prothrombin, and PAR1 mRNA expression was detected in isolated neuroretinas. Thrombin activity was elevated by nearly four-fold in mouse neuroretinas following KCl depolarization (0.012 vs. 0.044 mu/mL, p = 0.0497). The intrinsic expression of coagulation factors in the isolated neuroretina together with a functional increase in thrombin activity following KCl depolarization may suggest a role for the PAR1/thrombin pathway in retinal function.

Suprachoroidal delivery of bevacizumab in rabbit in vivo eyes: Rapid distribution throughout the posterior segment.

PURPOSE: To test the in-vivo bio-distribution and safety of bevacizumab delivery into the suprachoroidal space (SCS) using a novel injection system in a large eye model. METHODS: Bevacizumab (1.25 mg) was injected into the vitreous (IVT, 50 µL, n = 12) or the SCS, (150 µL, n = 37) of live rabbits. Immunofluorescence and ELISA were used to assess bevacizumab distribution. Intraocular pressure (IOP) measurements, SD-OCT and fundus imaging, electroretinogram, and histology analysis were performed for safety assessment. RESULTS: Bevacizumab was observed throughout the choroid layers up to the retinal pigment epithelium (RPE), within 1 h following SCS injection. The Cmax of bevacizumab in the retina/choroid was 1043 ± 597 µg/gr tissue (mean ± standard error), 40-fold higher than in IVT injected eyes (p = 0.0339). One day following SCS injection, bevacizumab was detected throughout the posterior pole with a two-fold lower concentration. One week post-SCS injection, bevacizumab concentration in the retina/choroid dropped to 2.36 ± 1.32 µg/gr tissue (p = 0.034 vs. 1 h), with a half-life of 20 h. No suprachoroidal blebs, retinal detachment, hemorrhages, inflammation or changes in retinal function were observed up to 2 months following SCS injection. Elevated IOP (+16 mmHg) was observed two minutes post-SCS injection and spontaneously returned to baseline levels within 10 minutes. CONCLUSIONS: The novel injection system enabled a minimally invasive, safe, and consistent delivery of bevacizumab with rapid distribution throughout the choroid layers up to the RPE in large eyes. Large volumes of anti-angiogenic are delivered in close proximity to the retina due to the high volume distribution.

Ophthalmic emergency-room visits during the Covid-19 pandemic - a comparative study.

BACKGROUND: The goal of this study is to compare ophthalmic emergency room (OER) visits during the Coronavirus disease-19 (Covid-19) pandemic to those during a control period. METHODS: We compared all visits to the OER to Meir Medical Center in Israel, from March 15th to April 15th, 2020, during the Covid-19 pandemic and government mandated quarantine, to the same period in 2019. Factors analyzed were patient demographics, chief complaints, referral patterns, exam findings, treatments given, hospitalizations and surgical interventions. RESULTS: We included in this study 1311 visits of 1158 patients, 477 during the 2020 Covid-19 pandemic and 834 during the same period in 2019. The demographic distribution (age, gender, and ethnicity) was similar between the two periods. LogMAR visual acuity at presentation was worse during the Covid-19 pandemic (0.42 ± 0.6 and 0.34 ± 0.5 in 2020 and 2019 respectively; p = 0.025) and the number of emergent surgeries was higher (3.7% in 2020 vs 1.8% in 2019, p = 0.026). In 2019 there was a higher likelihood of involvement of both segments of the eye (4.82% versus 1.2%, p < 0.01) and more diagnoses were given to each patient (1 ± 0.5 versus 0.93 ± 0.35, p = 0.001; During the Covid - 19 pandemic medications (both topical and systemic) were prescribed more often (1.22 ± 0.95 in 2020 and 0.84 ± 0.67 in 2019, p < 0.001). CONCLUSIONS: OER visits were less frequent during the Covid - 19 pandemic as compared to 2019, though the demographics of the patients remained unchanged. Visits during the pandemic tended to be for more severe ocular conditions, with worse visual acuity at presentation and required more medical and surgical treatment which imply higher necessity of ocular evaluation. This analysis can aid healthcare resource management in similar scenarios in the future.

In vivo retinal imaging in translational regenerative research.

Regenerative translational studies must include a longitudinal assessment of the changes in retinal structure and function that occur as part of the natural history of the disease and those that result from the studied intervention. Traditionally, retinal structural changes have been evaluated by histological analysis which necessitates sacrificing the animals. In this review, we describe key imaging approaches such as fundus imaging, optical coherence tomography (OCT), OCT-angiography, adaptive optics (AO), and confocal scanning laser ophthalmoscopy (cSLO) that enable noninvasive, non-contact, and fast in vivo imaging of the posterior segment. These imaging technologies substantially reduce the number of animals needed and enable progression analysis and longitudinal follow-up in individual animals for accurate assessment of disease natural history, effects of interventions and acute changes. We also describe the benefits and limitations of each technology, as well as outline possible future directions that can be taken in translational retinal imaging studies.

Chromatic Pupilloperimetry Measures Correlate With Visual Acuity and Visual Field Defects in Retinitis Pigmentosa Patients.

Purpose: To evaluate the ability of chromatic pupilloperimetry to identify visual field (VF) defects in patients with retinitis pigmentosa (RP) and to test the correlation between pupilloperimetry impairment and retinal structural and functional measures. Methods: The pupil responses of 10 patients with RP (mean age, 41.3 ± 16.2 years) and 32 healthy age-similar controls (mean age, 50.7 ± 15.5 years) for 54 focal blue and red stimuli presented in a 24-2 VF were recorded. The pupilloperimetry measures were correlated with Humphrey VF mean deviation, best-corrected visual acuity, and ellipsoid zone area. Results: Substantially lower percentage of pupil contraction and maximal pupil contraction velocity (MCV) were recorded in patients with RP throughout the VF in response to blue and red stimuli. The mean absolute deviation (MADEV) in the latency of MCV (LMCV) was significantly larger in patients compared with controls for blue and red stimuli (P = 1.0 × 10-7 and P = 1.0 × 10-6, respectively). The LMCV MADEV differentiated between patients and controls with high specificity and sensitivity (area under the receiver operating characteristic curve, 0.987 and 0.973 for blue and red, respectively). The MADEV of LMCV for blue stimuli correlated with best-corrected visual acuity (ρ = 0.938, P = 5.9 × 10-5) and ellipsoid zone area (ρ = -0.857; P = 0.002). The MADEV of LMCV for red stimuli correlated with Humphrey VF mean deviation (ρ = -0.709; P = 0.022). Minimizing the test to 15 targets maintained a diagnosis of retinal damage in patients with RP with high sensitivity and specificity (area under the receiver operating characteristic curve, 0.927). Conclusions: The chromatic pupilloperimetry measures significantly correlated with retinal function and structure in patients with RP at various disease stages. Translational Relevance: Chromatic pupilloperimetry may enable objective assessment of visual field defects and visual acuity in RP.

Efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid using a blunt adjustable depth injector.

PURPOSE: To evaluate the efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid (EVSC) in rabbit eyes in vivo using a blunt adjustable depth injector. METHODS: Indocyanine green (ICG) was injected in the superior-temporal quadrant, 2 mm posterior to the limbus at increasing volumes (0.1-0.3 ml) into the EVSC of New Zealand rabbit eyes in vivo. Intraocular pressure (IOP) measurements, spectral domain optical coherence tomography (SD-OCT), fundus imaging and histology analysis were performed to assess the safety and efficacy of the injection. RESULTS: Volumes up to 0.3 ml were administered consistently. ICG injection was successfully monitored in vivo using infrared fundus imaging and SD-OCT. ICG was detected across the EVSC compartment, reaching the retinal pigment epithelium, optic nerve head and visual streak. Injection of 0.3 ml yielded maximal dye distribution with a coverage area of 61.8% ± 6.7% (mean ± standard error, SE) of the posterior segment. Maximal IOP elevation was recorded 5 min following injection of 0.2 and 0.3 ml ICG (+ 20.0 mmHg, + 19.4 mmHg, respectively). Twenty minutes post-injection, the IOP was < 15 mmHg in all injection volumes. No retinal detachment or hemorrhages were detected in any of the injected eyes. CONCLUSIONS: This study demonstrates consistent and safe delivery of large volumes within the EVSC using a blunt adjustable depth injector that distributes the dye over 60% of the retinal surface. This injection system may offer a minimally invasive and easy way to deliver large volumes of pharmaceuticals into the posterior segment.

High-intensity Focused Ultrasound Treatment in Moderate Glaucoma Patients: Results of a 2-Year Prospective Clinical Trial.

PRECIS: Ultrasound Cyclo Plasty (UCP) treatment using high-intensity focused ultrasound (HIFU) is an effective and safe therapy to reduce intraocular pressure (IOP) in moderate glaucoma patients as was measured during a 2-year follow-up period. PURPOSE: The purpose of this study was to evaluate the long-term safety and efficacy of the UCP procedure using HIFU in moderate glaucoma patients. PATIENTS AND METHODS: A prospective interventional noncomparative study was carried out. Fifteen patients (15 eyes) with moderate open-angle glaucoma were enrolled. All eyes were treated with UCP-HIFU. A thorough ophthalmic examination and IOP measurements were performed before the UCP-HIFU procedure and at 1 day, 1 week, 4 weeks, 3 months, 6 months, 1 year, and 2 years after the procedure. The primary outcome was defined as a surgical success (IOP reduction of 20% or ≥5 mm Hg) at the last follow-up visit. The secondary outcomes were the mean IOP at each follow-up visit, number of medications used, complications profile, and reinterventions. RESULTS: The mean preoperative IOP at baseline was 26.8±5.0 mm Hg. All patients had a positive response and a lower IOP after treatment, with a relatively stable 31% reduction in IOP during the follow-up period. A significant reduction in IOP was observed at all postprocedure examination points (P<0.01), with a mean 17.6±4.4 mm Hg at 2 years after the procedure (P=0.005). Surgical success was achieved in 87% of the patients at their last follow-up visit. There was a nonsignificant decrease in the mean number of glaucoma medications from 2.5±0.8 to 2.0±1.0 at 2 years (P=0.48). No major intraoperative or postoperative complications were noted. CONCLUSION: UCP-HIFU treatment is an effective, safe, and well-tolerated method to reduce IOP in patients with moderate glaucoma.

Myopia and Childhood Migration: A Study of 607 862 Adolescents.

PURPOSE: Immigration studies can shed light on myopia development and reveal high-risk populations. To this end, we investigated the association among immigration, age at immigration, and myopia occurrence during adolescence. DESIGN: Population-based, retrospective, cross-sectional study. PARTICIPANTS: Six hundred seven thousand eight hundred sixty-two adolescents, Israeli born and immigrants, with origins in the former Union of Soviet Socialist Republics (USSR), Ethiopia, or Israel, assessed for medical fitness for mandatory military service at 17 years of age between 1993 and 2016. METHODS: Myopia and high myopia were defined based on right eye refractive data. Age at immigration was categorized into 0 to 5 years of age, 6 to 11 years of age, and 12 to 19 years of age. Univariate and multivariate logistic regression models were created. Myopia odds ratios (ORs) were calculated according to immigration status, with Israeli-born natives as controls. Next, myopia ORs were calculated according to age at immigration, with Israeli-born of same origin as controls. MAIN OUTCOME MEASURES: Myopia prevalence and ORs. RESULTS: Myopia was less prevalent among immigrants than Israeli-born controls. When stratified according to age at immigration, a decrease in myopia prevalence and ORs with increasing age at migration were observed, most prominent in immigrants arriving after 11 years of age, who also showed lower high-myopia ORs. The immigrants from the USSR and Ethiopia arriving after 11 years of age showed a myopia OR of 0.65 (95% confidence interval [CI], 0.63-0.67; P < 10-205) and 0.52 (95% CI, 0.46-0.58; P < 10-27) compared with the Israeli-born controls. Notably, Ethiopians arriving earlier than 5 years of age showed a 2-fold higher myopia OR than those migrating after 11 years of age. CONCLUSIONS: Immigrants arriving after 11 years of age showed markedly lower ORs for myopia and high myopia relative to Israeli-born controls or those arriving during early childhood, likely because of environmental and lifestyle changes. Differences between immigrants arriving up to 5 years of age and those arriving between 6 and 11 years of age were relatively smaller, suggesting exposures at elementary school age play a greater role in this population.

Repetitive magnetic stimulation protects corneal epithelium in a rabbit model of short-term exposure keratopathy.

PURPOSE: To investigate the effect of repetitive magnetic stimulation (RMS) on corneal epithelial permeability in a rabbit model of exposure keratopathy. METHODS: 61 female New Zealand White (NZW) rabbits were treated on one eye with repetitive magnetic stimulation (RMS) at a frequency of 20 Hz for 15 min. The other eye was untreated. Rabbit eyes were kept open for 2 h to induce acute corneal desiccation. The extent of fluorescein corneal staining was evaluated using EpiView software and the concentration of fluorescein in the anterior chamber was determined by a fluorometer. Safety was evaluated by electroretinogram, spectral domain optical coherence tomography (SD-OCT) and histopathology. Expression pattern of corneal cell markers was determined by immunofluorescence. RESULTS: A significant decrease in fluorescein concentration in the anterior chamber (54 ±â€¯8.4 ng/ml vs. 146.5 ±â€¯18.6 ng/ml, p = 0.000001) and in corneal surface fluorescein staining score (1.7 ±â€¯0.2 vs. 4.6 ±â€¯0.6, p = 0.00001) was obtained in RMS-treated eyes compared with control eyes, respectively. RMS treatment reduced by nearly 4 fold the percentage of corneal area with epithelial erosions by anterior segment SD-OCT. The therapeutic effect was maintained for at least 3 months. Increased expression of epithelial tight junction protein Zo-1 was observed in treated eyes. SD-OCT and histopathology analysis revealed no pathological changes in the treated or non-treated eyes. CONCLUSIONS: RMS treatment decreases epithelial corneal erosions in a rabbit model of exposure keratopathy, with no indication of pathological changes. RMS may present a novel treatment for protection of corneal epithelium from desiccation.

Anterior-Segment Optical Coherence Tomography-Guided Measurement Of A Melting Ulcer For Follow-Up Of Corneoscleral Thinning Progression.

PURPOSE: To evaluate the feasibility of using anterior-segment optical coherence tomography (AS-OCT) for three-dimensional assessment of corneoscleral thinning progression in ulcers after pterygium removal. METHODS: A patient with corneoscleral melting after pterygium removal surgery and mitomycin C treatment was evaluated using AS-OCT imaging of the corneoscleral ulcer at five consecutive time points, up to 2 years. AS-OCT scans of 8.3×5.6 mm (15°×10°) containing 41 B-scans spaced 139 µm apart were performed monthly for 4 months and then at 2 years following pterygium removal. A single B-scan was comprised of 768 A-scans. Ten B-scans of the same position were averaged in a single AS-OCT image. The area of ulcer's section (AUS) was measured in seven fixed landmarks through a horizontally aligned plane in order to provide an estimation of the three-dimensional size of the lesion. RESULTS: The AUS in the two superior locations increased during the follow-up period to an average of 114% at 2 years compared to the initial visit. In the other five locations (three midline and two inferior), the AUS decreased and was on average 64% in the midline and 29% in the inferior locations at 24 months. CONCLUSION: AS-OCT provided a readily available assessment of the lesion's three-dimensional size during repeated follow-ups and identification of localized areas at higher risk for perforation. This method may potentially be useful for corneal surface pathologies requiring repeated follow-ups and may aid in decision-making regarding corneal thickness based on an accurate measurement.

Microarchitecture of Schlemm Canal Before and After Cataract Extraction Surgery.

PRECIS: Schlemm canal (SC) expands after cataract extraction (CE), both in the area and in volume by 25% as was measured using enhanced-depth imaging optical coherent tomography (EDI-OCT) in patients before and 1 week after CE. PURPOSE: This study aims to characterize the structural and volume changes on the microstructure of SC in patients before and after uneventful phacoemulsification CE by using EDI-OCT. MATERIALS AND METHODS: Forty-one serial horizontal EDI-OCT B-scans (interval between B-scans, 69 µm) were obtained in the nasal corneoscleral limbus before and 1 week after CE. The structure of aqueous channels, conjunctival blood vessels and iris anatomy in each scan were used as landmarks to select for overlapping scans taken before and following CE. The SC cross-section area was measured in each of the selected scans and SC volume was determined following a 3-dimensional reconstruction. RESULTS: Eleven eyes (6 females and 5 males) were imaged successfully before and after CE. Mean age was 70.54±11.38 years. The mean axial length was 23.10±0.87 mm. After CE, the mean best-corrected visual acuity in logMAR improved from 0.4±0.13 to 0.2±0.13 (P=0.028). There was no significant change in the mean intraocular pressure before and after CE (15.09±1.33 to 15.0±2.16 mm Hg; P=0.39). The mean SC cross-section area increased by 25%, from 4744±376 to 5941±1048 µm (P<0.001). SC volume in the analyzed region increased by 25% from 6,641,473±585,954 to 8,317,909±1,328,809 µm (P<0.001). CONCLUSION: CE expands SC dimensions in healthy eyes. EDI-OCT imaging of SC may prove useful in the evaluation of the SC dimensions in vivo before and after CE.

Blue Autofluorescence Fundus Imaging for Monitoring Retinal Degeneration in Royal College of Surgeons Rats.

PURPOSE: Development of a method for noninvasive longitudinal follow-up of retinal degeneration in the whole retina for Royal College of Surgeons (RCS) rats, a commonly used model of retinitis pigmentosa associated with mutations in the MER-proto-oncogene tyrosine kinase (MERTK) gene. METHODS: Pigmented RCS rats at postnatal (p) days p28 to p84 were subjected to a biweekly spectral-domain optical coherence tomography (SD-OCT), blue laser fundus autofluorescence (BL-FAF) imaging, and multicolor fundus imaging. Wild-type (WT; Long Evans) rats were tested as control. RESULTS: Hyperautofluorescence developed throughout the fundus at p42, concomitant with a significant increase in SD-OCT thickness and reflectivity of the debris zone (DZ) layer as well as thinning of the photoreceptor outer nuclear layer (ONL). From p56 to p84, discrete hypofluorescent lesions surrounded by hyperfluorescent flecks were demonstrated around the optic disc that gradually spread throughout the retina. The hypofluorescent lesions were associated with loss of ONL and gradual thinning of the DZ layer. No hypofluorescent BL-FAF lesions were observed in WT rats. CONCLUSIONS: This study suggests that BL-FAF imaging may present a new method for noninvasive longitudinal follow-up of retinal degeneration in nearly the whole retina in RCS rats. TRANSLATIONAL RELEVANCE: A clinical test was developed that may be implemented in translational studies in the RCS rat model of MERTK-associated retinitis pigmentosa.

Multimodal Assessment of Corneal Erosions Using Optical Coherence Tomography and Automated Grading of Fluorescein Staining in a Rabbit Dry Eye Model.

PURPOSE: To evaluate the potential use of anterior segment spectral domain optical coherence tomography (AS-SD-OCT) combined with an automated grading of fluorescein staining for assessment of corneal erosions in a rabbit short-term dry eye model. METHODS: Twenty-one New Zealand white rabbits were anesthetized and eyes were kept open for 140 minutes to induce acute corneal desiccation. Rectangular scans of the cornea were performed using Spectralis AS-SD-OCT. Total corneal thickness, corneal epithelial thickness, and the percentage of epithelial erosion area (PEEA) were evaluated. Corneas were stained with fluorescein and graded automatically using EpiView and semi-automatically using ImageJ. Spearman's rank-order correlations were calculated to compare the AS-SD-OCT PEEA and the two corneal staining scores. RESULTS: Eye desiccation resulted in corneal epithelium erosions that covered 0.67% to 14.2% of the central cornea (mean ± SD: 3.95% ± 3.2%) by AS-SD-OCT. The percentage of corneal area positively stained with fluorescein ranged from 0.24% to 38.01% (mean ± SD: 12.24% ± 9.7%) by using ImageJ, correlating with the AS-SD-OCT PEEA (Spearman's ρ, 0.574; P = 0.007). The EpiView score ranged from 0.5 to 10.17 and was better correlated with the AS-SD-OCT PEEA score (Spearman's ρ, 0.795; P = 0.000017). CONCLUSIONS: Our study suggests that multimodal analysis of AS-SD-OCT and grading of fluorescein staining using EpiView software may enable quantitative assessment of corneal epithelial erosions in a rabbit short-term dry eye model. TRANSLATIONAL RELEVANCE: This multimodal imaging analysis may be applied for evaluation of superficial punctate keratitis associated with dry eye.