Retina

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Bowe T, Rahmani S, Yonekawa Y. Endoscopic Vitrectomy for Microcornea, Posterior Megalolenticonus, Persistent Fetal Vasculature, Coloboma Syndrome. Ophthalmology 2017;124(12):1742.
Breazzano MP, Nair AA, Arevalo FJ, Barakat MR, Berrocal AM, Chang JS, Chen A, Eliott D, Garg SJ, Ghadiali Q, Gong D, Grewal DS, Handa JT, Henderson M, Leiderman YI, Leng T, Mannina A, Mendel TA, Mustafi D, de Koo LOC, Patel SN, Patel TP, Prenner J, Richards P, Singh RP, Wykoff CC, Yannuzzi NA, Yu H, Modi YS, Chang S. Frequency of Urgent or Emergent Vitreoretinal Surgical Procedures in the United States During the COVID-19 Pandemic. JAMA Ophthalmol 2021;139(4):456-463.Abstract
Importance: The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time. Objective: To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic. Design, Setting, and Participants: Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders. Main Outcomes and Measures: Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic. Results: A total of 526 536 CPT codes were ascertained: 483 313 injections, 19 257 lasers or cryotherapy, 14 949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95% CI, -6.8 to -3.3 procedures; P < .001), for RD repairs, with a maximal 59.4% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95% CI, -2.7 to -1.4 repairs; P < .001), and for other vitrectomies, with a maximal 84.3% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95% CI, -3.3 to -1.8 other vitrectomies; P < .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment. Conclusions and Relevance: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.
Brodowska K, Stryjewski TP, Papavasileiou E, Chee YE, Eliott D. Validation of the Retinal Detachment after Open Globe Injury (RD-OGI) Score as an Effective Tool for Predicting Retinal Detachment. Ophthalmology 2017;124(5):674-678.Abstract

PURPOSE: The Retinal Detachment after Open Globe Injury (RD-OGI) Score is a clinical prediction model that was developed at the Massachusetts Eye and Ear Infirmary to predict the risk of retinal detachment (RD) after open globe injury (OGI). This study sought to validate the RD-OGI Score in an independent cohort of patients. DESIGN: Retrospective cohort study. PARTICIPANTS: The predictive value of the RD-OGI Score was evaluated by comparing the original RD-OGI Scores of 893 eyes with OGI that presented between 1999 and 2011 (the derivation cohort) with 184 eyes with OGI that presented from January 1, 2012, to January 31, 2014 (the validation cohort). METHODS: Three risk classes (low, moderate, and high) were created and logistic regression was undertaken to evaluate the optimal predictive value of the RD-OGI Score. A Kaplan-Meier survival analysis evaluated survival experience between the risk classes. MAIN OUTCOME MEASURES: Time to RD. RESULTS: At 1 year after OGI, 255 eyes (29%) in the derivation cohort and 66 eyes (36%) in the validation cohort were diagnosed with an RD. At 1 year, the low risk class (RD-OGI Scores 0-2) had a 3% detachment rate in the derivation cohort and a 0% detachment rate in the validation cohort, the moderate risk class (RD-OGI Scores 2.5-4.5) had a 29% detachment rate in the derivation cohort and a 35% detachment rate in the validation cohort, and the high risk class (RD-OGI scores 5-7.5) had a 73% detachment rate in the derivation cohort and an 86% detachment rate in the validation cohort. Regression modeling revealed the RD-OGI to be highly discriminative, especially 30 days after injury, with an area under the receiver operating characteristic curve of 0.939 in the validation cohort. Survival experience was significantly different depending upon the risk class (P < 0.0001, log-rank chi-square). CONCLUSIONS: The RD-OGI Score can reliably predict the future risk of developing an RD based on clinical variables that are present at the time of the initial evaluation after OGI.

Brown A, Cousins H, Cousins C, Esquenazi K, Elze T, Harris A, Filipowicz A, Barna L, Yonwook K, Vinod K, Chadha N, Altman RB, Coote M, Pasquale LR. Deep Learning for Localized Detection of Optic Disc Hemorrhages. Am J Ophthalmol 2023;255:161-169.Abstract
PURPOSE: To develop an automated deep learning system for detecting the presence and location of disc hemorrhages in optic disc photographs. DESIGN: Development and testing of a deep learning algorithm. METHODS: Optic disc photos (597 images with at least 1 disc hemorrhage and 1075 images without any disc hemorrhage from 1562 eyes) from 5 institutions were classified by expert graders based on the presence or absence of disc hemorrhage. The images were split into training (n = 1340), validation (n = 167), and test (n = 165) datasets. Two state-of-the-art deep learning algorithms based on either object-level detection or image-level classification were trained on the dataset. These models were compared to one another and against 2 independent glaucoma specialists. We evaluated model performance by the area under the receiver operating characteristic curve (AUC). AUCs were compared with the Hanley-McNeil method. RESULTS: The object detection model achieved an AUC of 0.936 (95% CI = 0.857-0.964) across all held-out images (n = 165 photographs), which was significantly superior to the image classification model (AUC = 0.845, 95% CI = 0.740-0.912; P = .006). At an operating point selected for high specificity, the model achieved a specificity of 94.3% and a sensitivity of 70.0%, which was statistically indistinguishable from an expert clinician (P = .7). At an operating point selected for high sensitivity, the model achieves a sensitivity of 96.7% and a specificity of 73.3%. CONCLUSIONS: An autonomous object detection model is superior to an image classification model for detecting disc hemorrhages, and performed comparably to 2 clinicians.
Brydon EM, Bronstein R, Buskin A, Lako M, Pierce EA, Fernandez-Godino R. AAV-Mediated Gene Augmentation Therapy Restores Critical Functions in Mutant PRPF31 iPSC-Derived RPE Cells. Mol Ther Methods Clin Dev 2019;15:392-402.Abstract
Retinitis pigmentosa (RP) is the most common form of inherited vision loss and is characterized by degeneration of retinal photoreceptor cells and the retinal pigment epithelium (RPE). Mutations in pre-mRNA processing factor 31 () cause dominant RP via haploinsufficiency with incomplete penetrance. There is good evidence that the diverse severity of this disease is a result of differing levels of expression of the wild-type allele among patients. Thus, we hypothesize that -related RP will be amenable to treatment by adeno-associated virus (AAV)-mediated gene augmentation therapy. To test this hypothesis, we used induced pluripotent stem cells (iPSCs) with mutations in and differentiated them into RPE cells. The mutant iPSC-RPE cells recapitulate the cellular phenotype associated with the PRPF31 pathology, including defective cell structure, diminished phagocytic function, defects in ciliogenesis, and compromised barrier function. Treatment of the mutant iPSC-RPE cells with AAV- restored normal phagocytosis and cilia formation, and it partially restored structure and barrier function. These results suggest that AAV-based gene therapy targeting RPE cells holds therapeutic promise for patients with -related RP.
Bujakowska KM, Liu Q, Pierce EA. Photoreceptor Cilia and Retinal Ciliopathies. Cold Spring Harb Perspect Biol 2017;9(10)Abstract
Photoreceptors are sensory neurons designed to convert light stimuli into neurological responses. This process, called phototransduction, takes place in the outer segments (OS) of rod and cone photoreceptors. OS are specialized sensory cilia, with analogous structures to those present in other nonmotile cilia. Deficient morphogenesis and/or dysfunction of photoreceptor sensory cilia (PSC) caused by mutations in a variety of photoreceptor-specific and common cilia genes can lead to inherited retinal degenerations (IRDs). IRDs can manifest as isolated retinal diseases or syndromic diseases. In this review, we describe the structure and composition of PSC and different forms of ciliopathies with retinal involvement. We review the genetics of the IRDs, which are monogenic disorders but genetically diverse with regard to causality.
Bulka CM, Dammann O, Santos HP, VanderVeen DK, Smeester L, Fichorova R, O'Shea MT, Fry RC. Placental CpG Methylation of Inflammation, Angiogenic, and Neurotrophic Genes and Retinopathy of Prematurity. Invest Ophthalmol Vis Sci 2019;60(8):2888-2894.Abstract
Purpose: Extremely preterm infants are at increased risk for retinopathy of prematurity (ROP). We previously identified several inflammatory proteins that were expressed early in life and are associated with an increased risk of ROP and several angiogenic and neurotrophic growth factors in the neonatal systemic circulation that are associated with a lower risk of ROP. In this paper, we report the results of a set of analyses designed to test the hypothesis that placental CpG methylation levels of 12 inflammation-, angiogenic-, and neurotrophic-associated genes predict the occurrence of prethreshold ROP in extremely preterm newborns. Methods: We used placental CpG methylation data from 395 newborns from the Extremely Low Gestational Age Newborns study. Results: Multivariable regression models revealed that placental DNA methylation of 16 CpG sites representing 8 genes were associated with prethreshold ROP. Specifically, CpG methylation in the serum amyloid A SAA1 and SAA2, brain-derived neurotrophic factor (BDNF), myeloperoxidase (MPO), C-reactive protein (CRP), angiopoietin 1 (ANGPT1), and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) genes was associated with a lower risk of prethreshold ROP. Conversely, CpG methylation at three probes within tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and in two alternative probes within the BDNF and ANGPT1 genes was associated with an increased risk of ROP. Conclusions: CpG methylation may be a useful marker for improving ROP prediction, opening the opportunity for early intervention to lessen disease severity.
Busch C, Zur D, Fraser-Bell S, Laíns I, Santos AR, Lupidi M, Cagini C, Gabrielle P-H, Couturier A, Mané-Tauty V, Giancipoli E, Ricci GD'A, Cebeci Z, Rodríguez-Valdés PJ, Chaikitmongkol V, Amphornphruet A, Hindi I, Agrawal K, Chhablani J, Loewenstein A, Iglicki M, Rehak M, Rehak M. Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema. Acta Diabetol 2018;55(8):789-796.Abstract
AIMS: To compare functional and anatomical outcomes of continued anti-vascular endothelial growth factor (VEGF) therapy versus dexamethasone (DEX) implant in eyes with refractory diabetic macular edema (DME) after three initial anti-VEGF injections in a real-world setting. METHODS: To be included in this retrospective multicenter, case-control study, eyes were required: (1) to present with early refractory DME, as defined by visual acuity (VA) gain ≤ 5 letters or reduction in central subfield thickness (CST) ≤ 20%, after a loading phase of anti-VEGF therapy (three monthly injections) and (2) to treat further with (a) anti-VEGF therapy or (b) DEX implant. Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) at 12 months. Due to imbalanced baseline characteristics, a matched anti-VEGF group was formed by only keeping eyes with similar baseline characteristics as those in the DEX group. RESULTS: A total of 110 eyes from 105 patients were included (anti-VEGF group: 72 eyes, DEX group: 38 eyes). Mean change in VA at 12 months was - 0.4 ± 10.8 letters (anti-VEGF group), and + 6.1 ± 10.6 letters (DEX group) (P = 0.004). Over the same period, mean change in CST was + 18.3 ± 145.9 µm (anti-VEGF group) and - 92.8 ± 173.6 µm (DEX group) (P < 0.001). Eyes in the DEX group were more likely to gain ≥ 10 letters (OR 3.71, 95% CI 1.19-11.61, P = 0.024) at month 12. CONCLUSIONS: In a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12 months than those that continued treatment with anti-VEGF therapy.
Buskin A, Zhu L, Chichagova V, Basu B, Mozaffari-Jovin S, Dolan D, Droop A, Collin J, Bronstein R, Mehrotra S, Farkas M, Hilgen G, White K, Pan K-T, Treumann A, Hallam D, Bialas K, Chung G, Mellough C, Ding Y, Krasnogor N, Przyborski S, Zwolinski S, Al-Aama J, Alharthi S, Xu Y, Wheway G, Szymanska K, McKibbin M, Inglehearn CF, Elliott DJ, Lindsay S, Ali RR, Steel DH, Armstrong L, Sernagor E, Urlaub H, Pierce E, Lührmann R, Grellscheid S-N, Johnson CA, Lako M. Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat Commun 2018;9(1):4234.Abstract
Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause non-syndromic retinal disease. Here, we generate transcriptome profiles from RP11 (PRPF31-mutated) patient-derived retinal organoids and retinal pigment epithelium (RPE), as well as Prpf31 mouse tissues, which revealed that disrupted alternative splicing occurred for specific splicing programmes. Mis-splicing of genes encoding pre-mRNA splicing proteins was limited to patient-specific retinal cells and Prpf31 mouse retinae and RPE. Mis-splicing of genes implicated in ciliogenesis and cellular adhesion was associated with severe RPE defects that include disrupted apical - basal polarity, reduced trans-epithelial resistance and phagocytic capacity, and decreased cilia length and incidence. Disrupted cilia morphology also occurred in patient-derived photoreceptors, associated with progressive degeneration and cellular stress. In situ gene editing of a pathogenic mutation rescued protein expression and key cellular phenotypes in RPE and photoreceptors, providing proof of concept for future therapeutic strategies.
Butler NJ, Moradi A, Salek SS, Burkholder BM, Leung TG, Dunn JP, Thorne JE. Acute Retinal Necrosis: Presenting Characteristics and Clinical Outcomes in a Cohort of Polymerase Chain Reaction-Positive Patients. Am J Ophthalmol 2017;179:179-189.Abstract
PURPOSE: To identify determinants of adverse outcomes in acute retinal necrosis (ARN), presenting characteristics and incidence rates of vision loss and ocular complications in a cohort of polymerase chain reaction (PCR)-positive eyes were analyzed. DESIGN: Retrospective observational cohort study. METHODS: Forty-one eyes of 36 patients with clinically diagnosed ARN, PCR-positive for herpes simplex virus or varicella zoster virus and evaluated between January 2002 and June 2013, were included. Main outcome measures included incidence rates of vision loss and retinal detachment (RD). RESULTS: Presenting visual acuity was generally poor (20/50 to >20/200 in 27%; 20/200 or worse in 56%). The incidence rate of ≤20/200 was 0.66/eye-year (EY), (95% confidence interval [CI], 0.32/EY to 1.22/EY); the rate of light perception or no light perception vision was 0.07/EY (95% CI, 0.02/EY to 0.16/EY). During follow-up, 59% of eyes developed at least 1 RD (rate = 0.40/EY, 95% CI, 0.19/EY to 0.58/EY). Eyes with retinitis involving ≥25% of the retina at presentation detached at nearly 12 times the rate, as compared to those with <25% retinal involvement (0.70/EY vs 0.06/EY; P = .001). Development of an RD was the greatest determinant of adverse visual outcomes, with 4% of eyes, that had experienced at least 1 RD, achieving a best-corrected visual acuity of ≥20/40 compared to 53% of eyes that never detached (P = .0003). CONCLUSIONS: Poor outcomes in ARN were common in this cohort. RD confers the greatest risk of incident vision loss, and once 25% or more of the retina is involved the risk of RD and visual loss increases significantly.
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Cai S, Smith ME, Redenti SM, Wnek GE, Young MJ. Mouse retinal progenitor cell dynamics on electrospun poly (ϵ-caprolactone). J Biomater Sci Polym Ed 2012;23(11):1451-65.Abstract
Age-related macular degeneration, retinitis pigmentosa and glaucoma are among the many retinal degenerative diseases where retinal cell death leads to irreversible vision loss and blindness. Working toward a cell-replacement-based therapy for such diseases, a number of research groups have recently evaluated the feasibility of using retinal progenitor cells (RPCs) cultured and transplanted on biodegradable polymer substrates to replace damaged retinal tissue. Appropriate polymer substrate design is essential to providing a three-dimensional environment that can facilitate cell adhesion, proliferation and post-transplantation migration into the host environment. In this study, we have designed and fabricated a novel, ultra-thin electrospun poly(ϵ-caprolactone) (PCL) scaffold with microscale fiber diameters, appropriate porosity for infiltration by RPCs, and biologically compatible mechanical characteristics. We have verified that our electrospun PCL scaffold supports robust mouse RPC proliferation, adhesion, and differentiation in vitro, as well as migration into mouse retinal explants. These promising results make PCL a strong candidate for further development as a cell transplantation substrate in retinal regenerative research.
Cai LZ, Lin J, Starr MR, Obeid A, Ryan EH, Ryan C, Forbes NJ, Arias D, Ammar MJ, Patel LG, Capone A, Emerson GG, Joseph DP, Eliott D, Gupta OP, Regillo CD, Hsu J, Yonekawa Y, Yonekawa Y. PRO score: predictive scoring system for visual outcomes after rhegmatogenous retinal detachment repair. Br J Ophthalmol 2023;107(4):555-559.Abstract
BACKGROUND/AIMS: To compare risk factors for poor visual outcomes in patients undergoing primary rhegmatogenous retinal detachment (RRD) repair and to develop a scoring system. METHODS: Analysis of the Primary Retinal detachment Outcomes (PRO) study, a multicentre interventional cohort of consecutive primary RRD surgeries performed in 2015. The main outcome measure was a poor visual outcome (Snellen VA ≤20/200). RESULTS: A total of 1178 cases were included. The mean preoperative and postoperative logMARs were 1.1±1.1 (20/250) and 0.5±0.7 (20/63), respectively. Multivariable logistic regression identified preoperative risk factors predictive of poor visual outcomes (≤20/200), including proliferative vitreoretinopathy (PVR) (OR 1.26; 95% CI 1.13 to 1.40), history of antivascular endothelial growth factor (VEGF) injections (1.38; 1.11 to 1.71), >1-week vision loss (1.17; 1.08 to 1.27), ocular comorbidities (1.18; 1.00 to 1.38), poor presenting VA (1.06 per initial logMAR unit; 1.02 to 1.10) and age >70 (1.13; 1.04 to 1.23). The data were split into training (75%) and validation (25%) and a scoring system was developed and validated. The risk for poor visual outcomes was 8% with a total score of 0, 17% with 1, 29% with 2, 47% with 3, and 71% with 4 or higher. CONCLUSIONS: Independent risk factors were compared for poor visual outcomes after RRD surgery, which included PVR, anti-VEGF injections, vision loss >1 week, ocular comorbidities, presenting VA and older age. The PRO score was developed to provide a scoring system that may be useful in clinical practice.
Cakir B, Liegl R, Hellgren G, Lundgren P, Sun Y, Klevebro S, Löfqvist C, Mannheimer C, Cho S, Poblete A, Duran R, Hallberg B, Canas J, Lorenz V, Liu Z-J, Sola-Visner MC, Smith LEH, Hellström A. Thrombocytopenia is associated with severe retinopathy of prematurity. JCI Insight 2018;3(19)Abstract
Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (<100 × 109/l) at ≥30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
Carvalho LS, Xiao R, Wassmer SJ, Langsdorf A, Zinn E, Pacouret S, Shah S, Comander JI, Kim LA, Lim L, Vandenberghe LH. Synthetic Adeno-Associated Viral Vector Efficiently Targets Mouse and Nonhuman Primate Retina In Vivo. Hum Gene Ther 2018;29(7):771-784.Abstract
Gene therapy is a promising approach in the treatment of inherited and common complex disorders of the retina. Preclinical and clinical studies have validated the use of adeno-associated viral vectors (AAV) as a safe and efficient delivery vehicle for gene transfer. Retinal pigment epithelium and rods-and to a lesser extent, cone photoreceptors-can be efficiently targeted with AAV. Other retinal cell types however are more challenging targets. The aim of this study was to characterize the transduction profile and efficiency of in silico designed, synthetic Anc80 AAVs for retinal gene transfer. Three Anc80 variants were evaluated for retinal targeting in mice and primates following subretinal delivery. In the murine retina Anc80L65 demonstrated high level of retinal pigment epithelium and photoreceptor targeting with comparable cone photoreceptor affinity compared to other AAVs. Remarkably, Anc80L65 enhanced transduction kinetics with visible expression as early as day 1 and steady state mRNA levels at day 3. Inner retinal tropism of Anc80 variants demonstrated distinct transduction patterns of Müller glia, retinal ganglion cells and inner nuclear layer neurons. Finally, murine findings with Anc80L65 qualitatively translated to the Rhesus macaque in terms of cell targets, levels and onset of expression. Our findings support the use of Anc80L65 for therapeutic subretinal gene delivery.
Carvalho LS, Vandenberghe LH. Understanding Cone Photoreceptor Cell Death in Achromatopsia. Adv Exp Med Biol 2016;854:231-6.Abstract

Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.

Catomeris AJ, Ballios BG, Sangermano R, Wagner NE, Comander JI, Pierce EA, Place EM, Bujakowska KM, Huckfeldt RM. Novel RCBTB1 variants causing later-onset non-syndromic retinal dystrophy with macular chorioretinal atrophy. Ophthalmic Genet 2022;43(3):332-339.Abstract
BACKGROUND: Variants in RCBTB1 were recently described to cause a retinal dystrophy with only eight families described to date and a predominant phenotype of macular atrophy and peripheral reticular degeneration. Here, we further evaluate the genotypic and phenotypic characteristics of biallelic RCBTB1-associated retinal dystrophy in a North American clinic population. METHODS: A retrospective analysis of genetic and clinical features was performed in individuals with biallelic variants in RCBTB1. RESULTS: Three unrelated individuals of French-Canadian descent with rare biallelic RCBTB1 variants were identified. All individuals shared a novel p.(Ser342Leu) missense variant; one patient was homozygous whereas the other two each possessed a second unique novel variant p.(Gln120*) and p.(Pro224Leu). All three had macula-predominant disease with symptom onset in the fifth decade of life. CONCLUSION: This report adds to the genetic diversity of RCBTB1-associated disease. These cases confirm the later-onset, relative to many other retinal dystrophies, and macular focus of disease described in most cases to-date. They are thus a reminder of considering hereditary disease in the differential for later-onset macular atrophy.
Chan CSY, Lonfat N, Zhao R, Davis AE, Li L, Wu M-R, Lin C-H, Ji Z, Cepko CL, Wang S. Cell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors and -regulatory modules in the retina. Development 2020;147(14)Abstract
Transcription factors (TFs) are often used repeatedly during development and homeostasis to control distinct processes in the same and/or different cellular contexts. Considering the limited number of TFs in the genome and the tremendous number of events that need to be regulated, re-use of TFs is necessary. We analyzed how the expression of the homeobox TF, orthodenticle homeobox 2 (Otx2), is regulated in a cell type- and stage-specific manner during development in the mouse retina. We identified seven -regulatory modules (CRMs), among which the O5, O7 and O9 CRMs mark three distinct cellular contexts of Otx2 expression. We discovered that Otx2, Crx and Sox2, which are well-known TFs regulating retinal development, bind to and activate the O5, O7 or O9 CRMs, respectively. The chromatin status of these three CRMs was found to be distinct in different retinal cell types and at different stages. We conclude that retinal cells use a cohort of TFs with different expression patterns and multiple CRMs with different chromatin configurations to regulate the expression of Otx2 precisely.
Chantarasorn Y, Oellers P, Eliott D. Choroidal Thickness Is Associated with Delayed Subretinal Fluid Absorption after Rhegmatogenous Retinal Detachment Surgery. Ophthalmol Retina 2019;3(11):947-955.Abstract
PURPOSE: To investigate the association between choroidal thickness and persistent subretinal fluid (PSF) after surgery for recent-onset rhegmatogenous retinal detachment (RRD). DESIGN: Case-control study. PARTICIPANTS: Fourteen eyes with macula-off RRD (with fovea on and off) that achieved retinal reattachment on funduscopy and demonstrated PSF after surgery (PSF group) were compared with 62 eyes with macula-off RRD (with fovea on and off) that did not demonstrate PSF after surgery (non-PSF group). METHODS: The diagnosis of PSF was made by the detection of subretinal fluid pockets on OCT beyond 6 weeks after surgery. Covariates included baseline demographics, duration of RRD, area of RRD, foveal status, method of subretinal fluid drainage, retinal pigment epithelium (RPE) changes, and choroidal thickness in both eyes. Multivariate regression analysis was performed by adding gender, age, and pathologic myopia into the model. The secondary outcomes included postoperative vision and time to resolution of PSF. MAIN OUTCOME MEASURES: Subfoveal choroidal thickness in affected eyes, measured by enhanced depth imaging OCT images. RESULTS: The percentage of eyes that underwent vitrectomy, scleral buckle surgery, and pneumatic retinopexy were 71.4%, 14.3%, and 14.3% in the PSF group, respectively, and 87.1%, 11.3%, and 1.6% in the non-PSF group, respectively. Eyes with PSF showed significantly thicker subfoveal choroid than eyes without PSF (305±61 μm vs. 200±70 μm, respectively; adjusted difference, 78.6±19.1 μm; 95% confidence interval [CI], 40.3-116.8 μm; P < 0.001). The PSF group demonstrated a greater proportion of RPE changes in fellow eyes (30.8% vs. 1.7%; P = 0.03) and significantly worse best-corrected visual acuity at the 12-month follow-up (P = 0.03). Multiple logistic regression analysis revealed that choroidal thickness of 280 μm or more was a significant factor associated with the presence of PSF (adjusted odds ratio [AOR], 13.4; 95% CI, 3.1-34.7 [P = 0.001]. CONCLUSIONS: Persistent subretinal fluid is associated with increased subfoveal choroidal thickness in surgical and fellow eyes and with RPE changes in the fellow eye. This indicates that PSF likely belongs to the pachychoroid spectrum. In affected eyes, PSF tends to persist for more than 1 year and results in delayed visual recovery.
Chapman JJ, Heidary G, Gise R. An overview of peripapillary hyperreflective ovoid mass-like structures. Curr Opin Ophthalmol 2022;33(6):494-500.Abstract
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the ophthalmic findings associated with peripapillary hyperreflective ovoid mass-like structures (PHOMS) in both adult and pediatric patients. RECENT FINDINGS: PHOMS have recently been identified in a number of different ophthalmic disease entities ranging from nonpathologic to pathologic, including but not limited to anatomic abnormalities (tilting in myopia), optic nerve head drusen, optic disc edema from inflammation (optic neuritis, white dot syndromes), vascular insults (ischemic optic neuropathy, retinal vascular occlusion), and papilledema. The mechanism underlying the formation of PHOMS has not been fully elucidated although it has been hypothesized that PHOMS occur secondary to axoplasmic stasis from crowding at the optic nerve head. SUMMARY: Although the clinical significance of the presence of PHOMS remains unclear, PHOMS are associated with several disease processes. Understanding the mechanism behind their formation and their impact on optic nerve head structure and visual function may be relevant in patients with optic nerve head pathology. The presence of PHOMS may also correlate with disease severity and duration. Future studies to evaluate whether the formation of PHOMS may be useful as an early indicator of disease or a prognostic tool are warranted.
Chee YE, Eliott D. The Role of Vitrectomy in the Management of Fungal Endophthalmitis. Semin Ophthalmol 2017;32(1):29-35.Abstract

Fungal endophthalmitis is an important cause of vision loss worldwide with a large body of literature describing the treatment of the disease. The evidence supporting the use of pars plana vitrectomy in the management of fungal endophthalmitis is largely comprised of case reports and case series and demonstrates the important role of vitrectomy surgery. Vitrectomy can improve the likelihood of establishing the diagnosis, enhance the treatment of infection by removing fungal elements in the vitreous, aid in the removal of other inoculated intraocular structures, and is an important tool in the management of vision-threatening post-infectious sequelae like retinal detachment and epiretinal membrane.

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