July 2022

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Moussa O, Frank T, Valenzuela IA, Aliancy J, Gong D, De Rojas JO, Dagi Glass LR, Winn BJ, Cioffi GA, Chen RWS. Efficacy of Preoperative Risk Stratification on Resident Phacoemulsification Surgeries. Clin Ophthalmol 2022;16:2137-2144.Abstract
Purpose: To evaluate efficacy of a novel risk stratification system in minimizing resident surgical complications and to evaluate whether the system could be used to safely introduce cataract surgery to earlier levels of training. Materials and Methods: This is a retrospective cross-sectional study on 530 non-consecutive cataract cases performed by residents at Columbia University. Risk scores, preoperative best corrected visual acuity (BCVA), intraoperative complications, postoperative day 1 (POD1), and month 1 (POM1) exam findings were tabulated. The relationship between risk scores and POD1 and POM1 BCVA was modeled using linear regression. The relationship between risk scores and complication rates was modeled using logistic regression. Logistic regression was used to model the rates of complications across different levels of training. Rates of complications were compared between diabetic versus non-diabetic patients using t-tests. Results: Risk scores did not have significant association with intraoperative complications. Risk scores were predictive of corneal edema (OR = 1.36, p = 0.0032) and having any POM1 complication (OR = 1.20, p = 0.034). Risk scores were predictive of POD1 (β = 0.13, p < 0.0001) and POM1 (β = 0.057, p = 0.00048) visual acuity. There was no significant association between level of training and rates of intraoperative (p = 0.9) or postoperative complications (p = 0.06). Rates of intraoperative complication trended higher among diabetic patients but was not statistically significant (p = 0.2). Conclusion: Higher risk scores were predictive of prolonged corneal edema but not risk of intraoperative complications. Our risk stratification system allowed us to safely introduce earlier phacoemulsification surgery.
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Patel NA, Powers SDL, Parrish RK. Modernizing the American Journal of Ophthalmology: Social Media, Podcasts, and Digital Illustrations. Am J Ophthalmol 2022;239:ix-x.
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Salongcay RP, Aquino LAC, Salva CMG, Saunar AV, Alog GP, Sun JK, Peto T, Silva PS. Comparison of Handheld Retinal Imaging with ETDRS 7-Standard Field Photography for Diabetic Retinopathy and Diabetic Macular Edema. Ophthalmol Retina 2022;6(7):548-556.Abstract
PURPOSE: To compare nonmydriatic (NM) and mydriatic (MD) handheld retinal imaging with standard ETDRS 7-field color fundus photography (ETDRS photographs) for the assessment of diabetic retinopathy (DR) and diabetic macular edema (DME). DESIGN: Prospective, comparative, instrument validation study. SUBJECTS: A total of 225 eyes from 116 patients with diabetes mellitus. METHODS: Following a standardized protocol, NM and MD images were acquired using handheld retinal cameras (NM images: Aurora, Smartscope, and RetinaVue-700; MD images: Aurora, Smartscope, RetinaVue-700, and iNview) and dilated ETDRS photographs. Grading was performed at a centralized reading center using the International Clinical Classification for DR and DME. Kappa statistics (simple [K], weighted [Kw]) assessed the level of agreement for DR and DME. Sensitivity and specificity were calculated for any DR, referable DR (refDR), and vision-threatening DR (vtDR). MAIN OUTCOME MEASURES: Agreement for DR and DME; sensitivity and specificity for any DR, refDR, and vtDR; ungradable rates. RESULTS: Severity by ETDRS photographs: no DR, 33.3%; mild nonproliferative DR, 20.4%; moderate DR, 14.2%; severe DR, 11.6%; proliferative DR, 20.4%; no DME, 68.0%; DME, 9.3%; non-center involving clinically significant DME, 4.9%; center-involving clinically significant DME, 12.4%; and ungradable, 5.3%. For NM handheld retinal imaging, Kw was 0.70 to 0.73 for DR and 0.76 to 0.83 for DME. For MD handheld retinal imaging, Kw was 0.68 to 0.75 for DR and 0.77 to 0.91 for DME. Thresholds for sensitivity (0.80) and specificity (0.95) were met by NM images acquired using Smartscope and MD images acquired using Aurora and RetinaVue-700 cameras for any DR and by MD images acquired using Aurora and RetinaVue-700 cameras for refDR. Thresholds for sensitivity and specificity were met by MD images acquired using Aurora and RetinaVue-700 for DME. Nonmydriatic and MD ungradable rates for DR were 15.1% to 38.3% and 0% to 33.8%, respectively. CONCLUSIONS: Following standardized protocols, NM and MD handheld retinal imaging devices have substantial agreement levels for DR and DME. With mydriasis, not all handheld retinal imaging devices meet standards for sensitivity and specificity in identifying any DR and refDR. None of the handheld devices met the established 95% specificity for vtDR, suggesting that lower referral thresholds should be used if handheld devices must be utilized. When using handheld devices, the ungradable rate is significantly reduced with mydriasis and DME sensitivity thresholds are only achieved following dilation.
Selvan H, Gupta S, Wiggs JL, Gupta V. Juvenile-onset open-angle glaucoma - A clinical and genetic update. Surv Ophthalmol 2022;67(4):1099-1117.Abstract
Juvenile-onset open-angle glaucoma (JOAG) is a subset of primary open-angle glaucoma that is diagnosed before 40 years of age. The disease may be familial or non-familial, with proportions varying among different populations. Myocilin mutations are the most commonly associated. JOAG is characterized by high intraocular pressures (IOP), with many patients needing surgery. The mean age at diagnosis is in the 3rd decade, with a male preponderance. Myopia is a common association. The pathophysiology underlying the disease is immaturity of the conventional outflow pathways, which may or may not be observed on gonioscopy and anterior segment optical coherence tomography. The unique optic nerve head features include large discs with deep, steep cupping associated with high IOP-induced damage. Progression rates among JOAG patients are comparable to adult primary glaucomas, but as the disease affects younger patients, the projected disability from this disease is higher. Early diagnosis, prompt management, and life-long monitoring play an important role in preventing disease progression. Gene-based therapies currently under investigation offer future hope.
Silva PS, Liu D, Glassman AR, Aiello LP, Grover S, Kingsley RM, Melia M, Sun JK, Sun JK. ASSESSMENT OF FLUORESCEIN ANGIOGRAPHY NONPERFUSION IN EYES WITH DIABETIC RETINOPATHY USING ULTRAWIDE FIELD RETINAL IMAGING. Retina 2022;42(7):1302-1310.Abstract
PURPOSE: Evaluate association of retinal nonperfusion (NP) on ultrawide field (UWF) fluorescein angiography (FA) with diabetic retinopathy (DR) severity and predominantly peripheral lesions (PPL). METHODS: Multicenter observational study, 652 eyes (361 participants) having nonproliferative DR (NPDR) without center-involved diabetic macular edema in at least one eye. Baseline 200° UWF-color and UWF-FA images were graded by a central reading center for color-PPL and FA-PPL, respectively. UWF-FA was graded for NP index within concentric zones: posterior pole (<10 mm from fovea), midperiphery (10-15 mm), and far periphery (>15 mm). RESULTS: Baseline Early Treatment Diabetic Retinopathy Study DR severity was 31.7% no DR/mild NPDR, 24.1% moderate NPDR, 14.0% moderately severe NPDR, 25.6% severe/very severe NPDR, and 4.6% proliferative DR. Worse DR severity was associated with increased NP index overall (P = 0.002), in the posterior pole (P < 0.001), midperiphery (P < 0.001), and far periphery (P = 0.03). On average, 29.6% of imaged retinal NP was in the posterior pole, 33.7% in midperiphery, and 36.7% in far periphery. Increased NP index was associated with FA-PPL (P < 0.001) but not with color-PPL (P = 0.65). CONCLUSION: Approximately, 70% of NP in diabetic eyes is located outside the posterior pole. Increased NP is associated with the presence of FA-PPL, suggesting UWF-FA may better predict future DR worsening than UWF-color alone.
Singh RB, Yuksel E, Sinha S, Wang S, Taketani Y, Luznik Z, Yin J, Dohlman TH, Dana R. Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease. Ocul Surf 2022;Abstract
PURPOSE: To determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD). DESIGN: Retrospective cohort study. METHODS: We performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients. MAIN OUTCOME MEASURE: Prevalence of NK in chronic oGVHD. RESULTS: We identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14%. The mean age of oGVHD patients with NK was 62.6 ± 12.9 years; 48% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56%, 20%, and 24% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 ± 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients. CONCLUSIONS: The prevalence of NK in chronic oGVHD patients was 14% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.
Singhal S, Patel G, Singh RB, Goyal A, Avgush K, Koka J. Atezolizumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis and Takotsubo cardiomyopathy. BMJ Case Rep 2022;15(7)Abstract
Atezolizumab is a humanised monoclonal IgG1 antibody that is used in treating many solid malignancies. Endocrinopathies are known but a rare adverse event of these immunotherapeutic drugs. Autoimmune diabetes induced by atezolizumab has been rarely reported in the literature. We report the case of a woman in her eighth decade with no known history of diabetes who developed new-onset autoimmune diabetes and Takotsubo cardiomyopathy due to the adverse effects of atezolizumab therapy for hepatocellular carcinoma. We also review the characteristics and outcomes of cases previously reported in the literature.
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VanderVeen DK, Oke I, Nihalani BR. Deviations From Age-Adjusted Normative Biometry Measures in Children Undergoing Cataract Surgery: Implications for Postoperative Target Refraction and IOL Power Selection. Am J Ophthalmol 2022;239:190-201.Abstract
PURPOSE: To evaluate whether pediatric eyes that deviate from age-adjusted normative biometry parameters predict variation in myopic shift after cataract surgery. METHODS: This is a single institution longitudinal cohort study combining prospectively collected biometry data from normal eyes of children <10 years old with biometry data from eyes undergoing cataract surgery. Refractive data from patients with a minimum of 5 visits over ≥5 years of follow-up were used to calculate myopic shift and rate of refractive growth. Cataractous eyes that deviated from the middle quartiles of the age-adjusted normative values for axial length and keratometry were studied for variation in myopic shift and rate of refractive growth to 5 years and last follow-up visit. Multivariable analysis was performed to determine the association between myopic shift and rate of refractive growth and factors of age, sex, laterality, keratometry, axial length, intraocular lens power, and follow-up length. RESULTS: Normative values were derived from 100 eyes; there were 162 eyes in the cataract group with a median follow-up of 9.6 years (interquartile range: 7.3-12.2 years). The mean myopic shift ranged from 5.5 D (interquartile range: 6.3-3.5 D) for 0- to 2-year-olds to 1.0 D (interquartile range: 1.5-0.6 D) for 8- to 10-year-olds. Multivariable analysis showed that more myopic shift was associated with younger age (P < .001), lower keratometry (P = .01), and male gender (P = .027); greater rate of refractive growth was only associated with lower keratometry measures (P = .001). CONCLUSIONS: Age-based tables for intraocular lens power selection are useful, and modest adjustments can be considered for eyes with lower keratometry values than expected for age.
VanderVeen DK, McClatchey TS, McClatchey SK, Nizam A, Lambert SR, Lambert SR. Effective lens position and pseudophakic refraction prediction error at 10½ years of age in the Infant Aphakia Treatment Study. J AAPOS 2022;Abstract
BACKGROUND: The refraction prediction error (PE) for infants with intraocular lens (IOL) implantation is large, possibly related to an effective lens position (ELP) that is different than in adult eyes. If these eyes still have nonadult ELPs as they age, this could result in persistently large PE. We aimed to determine whether ELP or biometry at age 10½ years correlated with PE in children enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: We compared the measured refraction of eyes randomized to primary IOL implantation to the "predicted refraction" calculated by the Holladay 1 formula, based on biometry at age 10½ years. Eyes with incomplete data or IOL exchange were excluded. The PE (predicted - measured refraction) and absolute PE were calculated. Measured anterior chamber depth (ACD) was used to assess the effect of ELP on PE. Multiple regression analysis was performed on absolute PE versus axial length, corneal power, rate of refractive growth, refractive error, and best-corrected visual acuity. RESULTS: Forty-three eyes were included. The PE was 0.63 ± 1.68 D; median absolute PE, 0.85 D (IQR, 1.83 D). The median absolute PE was greater when the measured ACD was used to calculate predicted refraction instead of the standard A-constant (1.88 D [IQR, 1.72] D vs 0.85 D [IQR, 1.83], resp. [P = 0.03]). Absolute PE was not significantly correlated with any other parameter. CONCLUSIONS: Variations in ELP did not contribute significantly to PE 10 years after infant cataract surgery.
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Wang Y, Jacobs DS. Role of therapeutic contact lenses in management of corneal disease. Curr Opin Ophthalmol 2022;33(4):306-310.Abstract
PURPOSE OF REVIEW: The current review highlights areas of innovation and research in the use of contact lenses in the treatment of corneal ectasia and ocular surface disease. RECENT FINDINGS: A series of academic reports were published by a committee of experts reviewing evidence-based practice patterns of contact lens use. There continues to be active research in the use of contact lenses in the management of keratoconus, including mini-scleral lenses, custom impression-based scleral lenses and wavefront-guided scleral lenses. Recent reports on contact lenses for ocular surface disease were primarily reviews, retrospective case reports or case series, with publications on contact lens use in corneal epithelial defects, graft-vs.-host disease, limbal stem cell deficiency and neurotrophic keratitis. There are recent publications on advances in drug-eluting contact lenses. SUMMARY: Corneal specialists should be aware of current advances in the field of contact lens expanding their use in corneal ectasia and ocular surface disease.
Wang J, Zhao L, Gu X, Xue Y, Wang S, Xiao R, Vandenberghe LH, Peng KA, Shu Y, Li H. Efficient Delivery of Adeno-Associated Virus into Inner Ear In Vivo Through Trans-Stapes Route in Adult Guinea Pig. Hum Gene Ther 2022;33(13-14):719-728.Abstract
Adeno-associated virus (AAV) are potent vectors to achieve treatment against hearing loss resulting from genetic defects. However, the effects of delivery routes and the corresponding transduction efficiencies for clinical applications remain elusive. In this study, we screened AAV vectors of three serotypes (AAV 8 and 9 and Anc80L65) into the inner ears of adult normal guinea pigs through trans-stapes (oval window) and trans-round window delivery routes in vivo. Trans-stapes route is akin to stape surgeries in humans. Then, auditory brainstem response (ABR) measurements were conducted to evaluate postoperative hearing, and inner ear tissues were harvested for transduction efficiency analysis. Results showed that AAV8 targeted partial inner hair cells (IHCs) in cochlear basal turn; AAV9 targeted IHCs in cochlear basal and second turn, also a part of vestibular hair cells (VHCs). In contrast, Anc80L65 contributed to green fluorescent proteins (GFP) signals of 80 - 95% IHCs and 67 - 91% outer hair cells (OHCs), as well as 69% VHCs through the trans-round window route, with 15-20 decibel (dB) ABR threshold shifts. And, through the trans-stapes (oval window) route, there were 71 - 90% IHCs and 42 - 81% OHCs, along with 64% VHCs demonstrating GFP positive, and the ABR threshold shifts were within 10 dB. This study revealed AAV could be efficiently delivered into mammalian inner ear cells in vivo through the trans-stapes (oval window) route with postoperative hearing preservation, and both delivery routes showed promise of virus-based clinical translation of hearing impairment treatment.
White E, Walsh L. The Impact of Occlusion Therapy on Amblyopia Success Outcomes. J Binocul Vis Ocul Motil 2022;72(3):183-190.Abstract
PURPOSE: The recommended amount of occlusion therapy and amblyopia treatment success rates remains controversial. This study explores rates of occlusion therapy success and attempts to address limitations of previous literature. METHODS: A retrospective chart review was performed on patients with occlusion therapy outcomes from 2012 to 2019. Equal visual acuity (VA) or stable VA for three consecutive clinical visits, despite reported good compliance defined outcome VA. RESULTS: Results showed 90.3% of subjects obtained outcome distance VA of 0.3logMAR, 76% ≥0.3logMAR, 35% ≥0.2logMAR, and 6% ≥0.1logMAR in the amblyopic eye following treatment. Sixty-nine percent of the study population obtained equal vision following occlusion therapy. Only initial VA (amblyopic eye) and initial interocular visual optotype difference at distance predicted post-treatment success. CONCLUSION: These results support the conclusion that occlusion therapy, both PTO and FTO, can be effective in treating amblyopia when good compliance is maintained based on parental reports of compliance. Additionally, as VA gain was higher than in previous literature, it is important to continue treatment until VA is equal or three consecutive cycles of stable VA are obtained to ensure maximum VA improvement.
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Xu J, Baliutaviciute V, Swan G, Bowers AR. Driving With Hemianopia X: Effects of Cross Traffic on Gaze Behaviors and Pedestrian Responses at Intersections. Front Hum Neurosci 2022;16:938140.Abstract
Purpose: We conducted a driving simulator study to investigate the effects of monitoring intersection cross traffic on gaze behaviors and responses to pedestrians by drivers with hemianopic field loss (HFL). Methods: Sixteen HFL and sixteen normal vision (NV) participants completed two drives in an urban environment. At 30 intersections, a pedestrian ran across the road when the participant entered the intersection, requiring a braking response to avoid a collision. Intersections with these pedestrian events had either (1) no cross traffic, (2) one approaching car from the side opposite the pedestrian location, or (3) two approaching cars, one from each side at the same time. Results: Overall, HFL drivers made more (p < 0.001) and larger (p = 0.016) blind- than seeing-side scans and looked at the majority (>80%) of cross-traffic on both the blind and seeing sides. They made more numerous and larger gaze scans (p < 0.001) when they fixated cars on both sides (compared to one or no cars) and had lower rates of unsafe responses to blind- but not seeing-side pedestrians (interaction, p = 0.037). They were more likely to demonstrate compensatory blind-side fixation behaviors (faster time to fixate and longer fixation durations) when there was no car on the seeing side. Fixation behaviors and unsafe response rates were most similar to those of NV drivers when cars were fixated on both sides. Conclusion: For HFL participants, making more scans, larger scans and safer responses to pedestrians crossing from the blind side were associated with looking at cross traffic from both directions. Thus, cross traffic might serve as a reminder to scan and provide a reference point to guide blind-side scanning of drivers with HFL. Proactively checking for cross-traffic cars from both sides could be an important safety practice for drivers with HFL.
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Yonamine S, Ton L, Rose-Nussbaumer J, Ying G-S, Ahmed IIK, Chen TC, Weiner A, Gedde SJ, Han Y. Survey of the American Glaucoma Society Membership on Current Glaucoma Drainage Device Placement and Postoperative Corticosteroid Use. Clin Ophthalmol 2022;16:2305-2310.Abstract
Purpose: To assess practice patterns and opinions of glaucoma specialists regarding glaucoma drainage device tube shunt placement and post-operative anti-inflammatory medication use. We also assess the perceived need for a randomized control trial to compare them. Patients and Methods: An online survey was distributed to a group of glaucoma specialists from the American Glaucoma Society via the American Glaucoma Society forum from April to August 2021. Results: One hundred and twenty-eight responses were included. Ninety percent placed tubes in the anterior chamber. Sixty-one percent reported that evidence suggested the superiority of sulcus tube placement over the anterior chamber, whereas 34% reported there was not enough evidence to suggest superiority of either in preventing endothelial cell loss. Comparing these techniques for intraocular pressure control, 49% reported evidence suggested sulcus tube placement superiority whereas 46% reported there was not enough evidence. Over 40% of respondents reported that they were either unfamiliar with literature or that there was not enough evidence to support the superiority of difluprednate 0.05% over prednisolone 1% for post-operative use in preventing endothelial cell loss and for intraocular pressure control. Ninety percent and 81% of respondents respectively would benefit from randomized control trials comparing outcomes of anterior chamber vs sulcus tube placement and post-operative corticosteroid usage. Conclusion: Most glaucoma specialists surveyed place glaucoma drainage device tube in the anterior chamber over the sulcus. A randomized control trial to determine optimal tube placement and post-operative anti-inflammatory medication use for preventing endothelial cell loss would change current glaucoma drainage device practice patterns.
Yousefi S, Pasquale LR, Boland MV, Johnson CA. Machine-identified Patterns of Visual Field Loss and An Association with Rapid Progression in the Ocular Hypertension Treatment Study. Ophthalmology 2022;Abstract
PURPOSE: To identify patterns of visual field (VF) loss based on unsupervised machine learning and to identify patterns that are associated with rapid progression. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: A total of 2231 abnormal VFs from 205 eyes of 176 OHTS participants followed over approximately 16 years. METHODS: VFs were assessed by an unsupervised deep archetypal analysis algorithm as well as an OHTS certified VF reader to identify prevalent patterns of VF loss. Machine-identified patterns of glaucoma damage were compared against those patterns previously identified (expert-identified) in the OHTS in 2003. Based on the longitudinal VFs of each eye, VF loss patterns that were strongly associated with rapid glaucoma progression were identified. MAIN OUTCOME MEASURES: Machine-expert correspondence and type of patterns of VF loss associated with rapid progression. RESULTS: The average VF mean deviation (MD) at conversion to glaucoma was -2.7 dB (Standard Deviation (SD) = 2.4 dB) while the average MD of the eyes at the last visit was -5.2 dB (SD = 5.5 dB). Fifty out of 205 eyes had MD rate of -1 dB/year or worse and were considered rapid progressors. Eighteen machine-identified patterns of VF loss were compared with expert-identified patterns in which 13 patterns of VF loss were similar. The most prevalent expert-identified patterns included partial arcuate, paracentral, and nasal step defects, and the most prevalent machine-identified patterns included temporal wedge, partial arcuate, nasal step, and paracentral VF defects. One of the machine-identified patterns of VF loss predicted future rapid VF progression after adjustment for age, sex, and initial MD. CONCLUSIONS: An automated machine learning system can identify patterns of VF loss and could provide objective, and reproducible nomenclature for characterizing early signs of visual defects and rapid progression in patients with glaucoma.
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Zhu S, Zidan A, Pang K, Musayeva A, Kang Q, Yin J. Promotion of corneal angiogenesis by sensory neuron-derived calcitonin gene-related peptide. Exp Eye Res 2022;220:109125.Abstract
The normal cornea has no blood vessels but has abundant innervation. There is emerging evidence that sensory nerves, originated from the trigeminal ganglion (TG) neurons, play a key role in corneal angiogenesis. In the current study, we examined the role of TG sensory neuron-derived calcitonin gene-related peptide (CGRP) in promoting corneal neovascularization (CNV). We found that CGRP was expressed in the TG and cultured TG neurons. In the cornea, minimal CGRP mRNA was detected and CGRP immunohistochemical staining was exclusively co-localized with corneal nerves, suggesting corneal nerves are likely the source of CGRP in the cornea. In response to intrastromal suture placement and neovascularization in the cornea, CGRP expression was increased in the TG. In addition, we showed that CGRP was potently pro-angiogenic, leading to vascular endothelial cell (VEC) proliferation, migration, and tube formation in vitro and corneal hemangiogenesis and lymphangiogenesis in vivo. In a co-culture system of TG neurons and VEC, blocking CGRP signaling in the conditioned media of TG neurons led to decreased VEC migration and tube formation. More importantly, subconjunctival injection of a CGRP antagonist CGRP8-37 reduced suture-induced corneal hemangiogenesis and lymphangiogenesis in vivo. Taken together, our data suggest that TG sensory neuron and corneal nerve-derived CGRP promotes corneal angiogenesis.
van Zyl T, Yan W, McAdams AM, Monavarfeshani A, Hageman GS, Sanes JR. Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types. Proc Natl Acad Sci U S A 2022;119(29):e2200914119.Abstract
The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens, and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some disorders, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that compose these tissues, we generated an anterior segment cell atlas of the human eye using high-throughput single-nucleus RNA sequencing (snRNAseq). We profiled 195,248 nuclei from nondiseased anterior segment tissues of six human donors, identifying >60 cell types. Many of these cell types were discrete, whereas others, especially in the lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment, revealing that some cell types are unique to a single structure, whereas others are shared across tissues. The integrated cell atlas was then used to investigate cell type-specific expression patterns of more than 900 human ocular disease genes identified through either Mendelian inheritance patterns or genome-wide association studies.

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