Novel features of degenerative retinoschisis identified using ultra-widefield multicolor channels: A review of 139 eyes.

BACKGROUND/OBJECTIVE: To utilize ultra-widefield multimodal imaging (Optos PLC) to describe novel findings in degenerative retinoschisis. METHODS: This retrospective, non-comparative case series of degenerative retinoschisis received a waiver of consent from Advarra IRB, Protocol 00066379. Initial ultra-widefield pseudocolour, colour-separated, autofluorescence, and peripheral OCT imaging were analysed for characterizing features. RESULTS: In total, 139 eyes were included. A hyporeflective reticular pattern associated with retinoschisis was seen on pseudocolour images in 39% of cases, but visible in 53% on green-separated images. Fine hyper-reflective foci were observed in 49%. In 27%, retinoschisis was confirmed with OCT. CONCLUSIONS: Ultra-widefield pseudocolour and green-separated images are valuable for the diagnosis and characterization of degenerative retinoschisis. The findings described may prompt the evaluation of subtle retinoschisis with peripheral OCT.

Anesthesia for ophthalmic surgery: an educational review.

PURPOSE: Selecting an anesthetic agent for ophthalmic surgery has crucial implications for the surgeon, anesthesiologist, and patient. This educational review explores the common classes of anesthesia used in ophthalmology. Additionally, we discuss the considerations unique to cataract, glaucoma, strabismus, orbital, oculoplastic, and ocular trauma surgeries. METHODS: A comprehensive Embase search was performed using combinations of the subject headings "anesthesia", "eye surgery", "ophthalmology" and "cataract extraction", "glaucoma", "strabismus", "vitreoretinal surgery", "retina surgery", "eye injury", and "eyelid reconstruction". RESULTS: Topical anesthetics are the most commonly used form of ocular anesthesia, used in both an office and surgical setting, and carry a minimal side effect profile. Notably, topical anesthetics offer analgesia, but do not provide akinesia or amnesia. Regional blocks, such as are sub-Tenon's, peribulbar, and retrobulbar blocks, are used when akinesia is required in addition to analgesia. Recently, sub-Tenon's blocks have recently gained popularity due to their improved safety profile compared to other regional blocks. General anesthesia is considered for long, complex surgery, surgery in patients with multiple comorbidities, surgery in young pediatric patients, or surgery in patients intolerant to local or regional anesthetic. CONCLUSION: Anesthetizing the eye has rapidly evolved in recent years, supporting the safety, efficacy and comfort of ocular surgery. Since there are many viable options of anesthetics available for ophthalmic surgery, a robust understanding of the patients needs, the skill of the surgical team, and surgery-specific factors ought to be considered when creating an anesthetic plan for surgery.

Proof-of-Concept Analysis of a Deep Learning Model to Conduct Automated Segmentation of OCT Images for Macular Hole Volume.

BACKGROUND AND OBJECTIVE: To determine whether an automated artificial intelligence (AI) model could assess macular hole (MH) volume on swept-source optical coherence tomography (OCT) images. PATIENTS AND METHODS: This was a proof-of-concept consecutive case series. Patients with an idiopathic full-thickness MH undergoing pars plana vitrectomy surgery with 1 year of follow-up were considered for inclusion. MHs were manually graded by a vitreoretinal surgeon from preoperative OCT images to delineate MH volume. This information was used to train a fully three-dimensional convolutional neural network for automatic segmentation. The main outcome was the correlation of manual MH volume to automated volume segmentation. RESULTS: The correlation between manual and automated MH volume was R2 = 0.94 (n = 24). Automated MH volume demonstrated a higher correlation to change in visual acuity from preoperative to the postoperative 1-year time point compared with the minimum linear diameter (volume: R2 = 0.53; minimum linear diameter: R2 = 0.39). CONCLUSION: MH automated volume segmentation on OCT imaging demonstrated high correlation to manual MH volume measurements. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):208-214.].

Utilization of deep learning to quantify fluid volume of neovascular age-related macular degeneration patients based on swept-source OCT imaging: The ONTARIO study.

PURPOSE: To evaluate the predictive ability of a deep learning-based algorithm to determine long-term best-corrected distance visual acuity (BCVA) outcomes in neovascular age-related macular degeneration (nARMD) patients using baseline swept-source optical coherence tomography (SS-OCT) and OCT-angiography (OCT-A) data. METHODS: In this phase IV, retrospective, proof of concept, single center study, SS-OCT data from 17 previously treated nARMD eyes was used to assess retinal layer thicknesses, as well as quantify intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelium detachments (PEDs) using a novel deep learning-based, macular fluid segmentation algorithm. Baseline OCT and OCT-A morphological features and fluid measurements were correlated using the Pearson correlation coefficient (PCC) to changes in BCVA from baseline to week 52. RESULTS: Total retinal fluid (IRF, SRF and PED) volume at baseline had the strongest correlation to improvement in BCVA at month 12 (PCC = 0.652, p = 0.005). Fluid was subsequently sub-categorized into IRF, SRF and PED, with PED volume having the next highest correlation (PCC = 0.648, p = 0.005) to BCVA improvement. Average total retinal thickness in isolation demonstrated poor correlation (PCC = 0.334, p = 0.189). When two features, mean choroidal neovascular membranes (CNVM) size and total fluid volume, were combined and correlated with visual outcomes, the highest correlation increased to PCC = 0.695 (p = 0.002). CONCLUSIONS: In isolation, total fluid volume most closely correlates with change in BCVA values between baseline and week 52. In combination with complimentary information from OCT-A, an improvement in the linear correlation score was observed. Average total retinal thickness provided a lower correlation, and thus provides a lower predictive outcome than alternative metrics assessed. Clinically, a machine-learning approach to analyzing fluid metrics in combination with lesion size may provide an advantage in personalizing therapy and predicting BCVA outcomes at week 52.

Enface vitreous OCT 'worm holes': A novel finding in a patient with diffuse unilateral subacute neuroretinitis (DUSN).

PURPOSE: To describe a case of diffuse unilateral subacute neuroretinitis (DUSN), a rare condition that causes progressive vision loss following infection by a nematode using enface vitreous imaging. OBSERVATIONS: We present the clinical findings of a 37-year-old female, clinically diagnosed with DUSN after a non-invasive multimodal imaging approach that included MultiColor scanning laser imaging and enface vitreous OCT, which revealed the nematode body and lacunae created by worm migration, respectively. CONCLUSION AND IMPORTANCE: To our knowledge, this is the first reported case of lacunae visualized using enface vitreous optical coherence tomography (OCT), potentially marking the migration path of the nematode.

Feasibility of peripheral OCT imaging using a novel integrated SLO ultra-widefield imaging swept-source OCT device.

PURPOSE: To describe the feasibility of peripheral OCT imaging in retinal diseases using a novel full-field device. METHODS: A total of 134 consecutive eyes were referred and imaged on the Optos Silverstone swept-source OCT (SS-OCT) (Optos PLC; Dunfermline, UK). Scanning laser ophthalmoscope (SLO) images and the associated SS-OCT images were obtained in the posterior pole, mid-periphery or far periphery based on the nature of the referral and on new areas of interest observed in the optomap images at the time of imaging. RESULTS: A total of 134 eyes (96 patients) were enrolled in the study. One hundred and twenty-five eyes (91 patients) with 38 retinal pathologies were prospectively assessed and 9 eyes (5 patients) were excluded due to incomplete image acquisition. The average age of the subjects was 54 years (range 21-92 years). Thirty-nine out of 125 eyes (31%) had macular pathologies. Eighty-six out of 125 eyes (69%) had peripheral only pathologies, an area which cannot be visualized by standard OCT devices with a 50 degree field-of-view. CONCLUSIONS: The ability to capture peripheral pathologies using an integrated SLO-UWF imaging with full-field swept-source provided high-grade anatomical insight that confirmed the medical and surgical management in a majority of cases. Its use in the mid- and far periphery provides a holistic clinical picture, which can potentially aid in the understanding of various retinal pathologies.

A proof of concept study to evaluate the treatment response of aflibercept in wARMD using OCT-A (Canada study).

PURPOSE: To Utilize OCT-A to measure the change in size (mm2) and density (flow index) of choroidal neovascular membranes (CNVMs) from baseline to week 52 of treatment-naïve wet age-related macular degeneration (wARMD) patients receiving intravitreal aflibercept injections (IAI). METHODS: Patients were treated with IAI at baseline, month 1 and month 2 and then every other month for a total of 12 months. Along with clinical examination and best corrected visual acuity (BCVA), OCT-A 6- and 3-mm scans were acquired at every visit between May 2017 and January 2019. Data from baseline, week 12 and week 52 were analyzed prospectively and included in the final analysis. RESULTS: Twenty-five eyes from 23 patients were included in the study. The mean BCVA at baseline and week 52 increased from 20/125 to 20/80, respectively (p < 0.001). The mean CST at baseline and week 52 decreased from 330.48 to 222.40 µm, respectively (p < 0.001). 1Seventeen patients (18 eyes) completed all protocol-based 6 × 6 mm and 3 × 3 mm OCT-A scans. In this subgroup, 6-mm OCT-A scans revealed that the mean size of the CNVM before and after IAI was 1.21 mm2 and 0.56 mm2, respectively (p < 0.001), while the 3-mm OCT-A scans at baseline and week 52 demonstrated a decrease in mean size of the CNVM from 0.89 to 0.37 mm2, respectively (p < 0.001). The 6-mm perfusion density map revealed no difference at either time points. CONCLUSIONS: OCT-A provides a useful approach for monitoring and evaluating the treatment of intravitreal aflibercept for CNVMs. Mean size of CNVMs can be identified by 3- or 6-mm scans, but without machine learning, it requires extensive segmentation. While reproducibility and clear delineation of CNVMs in wARMD using OCT-A is challenging, OCT-A does offer the ability to monitor CNVM size changes during treatment and may offer another biomarker to assist in assessing treatment response.

Quantifiable In Vivo Imaging Biomarkers of Retinal Regeneration by Photoreceptor Cell Transplantation.

Purpose: Short-term improvements in retinal anatomy are known to occur in preclinical models of photoreceptor transplantation. However, correlative changes over the long term are poorly understood. We aimed to develop a quantifiable imaging biomarker grading scheme, using noninvasive multimodal confocal scanning laser ophthalmoscopy (cSLO) imaging, to enable serial evaluation of photoreceptor transplantation over the long term. Methods: Photoreceptor cell suspensions or sheets from rhodopsin-green fluorescent protein mice were transplanted subretinally, into either NOD.CB17-Prkdcscid/J or C3H/HeJ-Pde6brd1 mice. Multimodal cSLO imaging was performed serially for up to three months after transplantation. Imaging biomarkers were scored, and a grade was defined for each eye by integrating the scores. Image grades were correlated with immunohistochemistry (IHC) data. Results: Multimodal imaging enabled the extraction of quantitative imaging biomarkers including graft size, GFP intensity, graft length, on-target graft placement, intra-graft lamination, hemorrhage, retinal atrophy, and periretinal proliferation. Migration of transplanted material was observed. Changes in biomarker scores and grades were detected in 14/16 and 7/16 eyes, respectively. A high correlation was found between image grades and IHC parameters. Conclusions: Serial evaluation of multiple imaging biomarkers, when integrated into a per-eye grading scheme, enabled comprehensive tracking of longitudinal changes in photoreceptor cell grafts over time. The application of systematic multimodal in vivo imaging could be useful in increasing the efficiency of preclinical retinal cell transplantation studies in rodents and other animal models. Translational Relevance: By allowing longitudinal evaluation of the same animal over time, and providing quantifiable biomarkers, non-invasive multimodal imaging improves the efficiency of retinal transplantation studies in animal models. Such assays will facilitate the development of cell therapy for retinal diseases.

A NOVEL LARGE HOMOZYGOUS DELETION IN THE CELLULAR RETINALDEHYDE-BINDING PROTEIN GENE (RLBP1) IN A PATIENT WITH RETINITIS PUNCTATA ALBESCENS.

PURPOSE: To report the phenotypic and genotypic data of a patient with retinitis punctata albescens carrying a novel deletion in the RLBP1 gene. RESULTS: A woman of Iranian descent in her forties with a history of progressive visual deterioration since early childhood exhibited phenotypic features of retinitis punctata albescens with multiple white dots in the posterior pole and macular atrophy in both eyes. The microarray analysis identified a ∼2.160 kb homozygous deletion corresponding to a minimum deletion boundary of chr15q26.1:89,756,882-89,759,041/GRCh37 (hg19), which encompasses exon 6 of the RLBP1 gene. CONCLUSION: We describe a novel large homozygous deletion in the RLBP1 gene encoding the cellular retinaldehyde-binding protein in a patient of Iranian descent with retinitis punctata albescens. Genotype-phenotype studies may provide more information about the functions of the RLBP1 encoding proteins and the disease course, because RLBP1 mutations are associated with high phenotypic variability and are therefore a necessity for future tailored individual therapies.

A Novel Mutation in the Choroideremia Gene in a Turkish Family.

Choroideremia is an X-linked recessive genetic disorder caused by mutations in the CHM gene. It is a rare retinal dystrophy that manifests as nyctalopia and vision loss, progressing to blindness in later stages. We report a 21-year Turkish man who presented with nyctalopia for the past 4-5 years. His mother and maternal grandmother had similar, but less pronounced complaints. Fundus examination revealed pigmentary changes and retinal atrophy in both eyes. Optical coherence tomography showed outer retinal loss, with central island of preserved autofluorescence surrounded by absent autofluorescence on fundus autofluorescence examination. Goldmann visual fields were constricted. Microperimetry detected retinal sensitivity losses, and full-field electroretinogram demonstrated extinguished cone responses. Genetic analysis revealed a novel nonsense mutation in the CHM gene, namely p.E480X: c.1438G >T. The mutation causes a premature stop codon in exon 12. This is the first report of a G1438T mutation resulting in an E480X premature stop in the CHM gene.

Progression of retinitis pigmentosa on multimodal imaging: The PREP-1 study.

IMPORTANCE: It is important to establish reliable outcome measures to detect progression in retinitis pigmentosa (RP). BACKGROUND: To evaluate progression of RP using multimodal imaging, including spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and microperimetry (MP). DESIGN: Retrospective longitudinal study at a tertiary teaching hospital. PARTICIPANTS: 205 eyes of 106 patients with RP with 1 to 5 y of follow-up. METHODS: Demographics and visual acuity (VA) were recorded, and each modality was graded at baseline and every annual follow-up. SD-OCT was graded for the width of ellipsoid zone (EZ), FAF was graded for the diameter and area of the hyperautofluorescent ring (if present), and MP was graded for mean, central and paracentral sensitivity. Spearman's correlation was used to measure correlations at baseline. Mixed effects models were used to estimate the annual change of each parameter, adjusted for disease duration. MAIN OUTCOME MEASURES: Rate of progression. RESULTS: The median VA at baseline was 75 letters and was positively correlated with mean and central sensitivity (r: 0.372 and 0.394; P = 0.01 for both). All parameters (except paracentral sensitivity) were strongly correlated with each other (r: 0.673-0.991; P < 0.001 for all). The annual rates of change for each parameter were as follows: VA, -2.3 letters (P < 0.001); EZ, -151 µm (P < 0.001); ring diameter, -132 µm (P < 0.001); ring area, -0.4 mm2 (P < 0.001); mean sensitivity, -0.3 dB (P < 0.001); central sensitivity, -0.7 dB (P < 0.001); paracentral sensitivity, -0.4 dB (P < 0.001). CONCLUSIONS AND RELEVANCE: Structural and functional measures are well correlated in RP and can reliably measure disease progression within the course of a year.