UG1EY014231 Network Overview - PowerPoint Presentation

1. UG1EY014231Network Overview

2. DRCR Retina Network OverviewThe DRCR Retina Network's mission is to conduct high quality, collaborative clinical research that improves vision and quality of life for people with retinal diseases. The DRCR Retina Network supports the identification, design, and implementation of multicenter clinical research initiatives focused on retinal disorders. Principal emphasis is placed on clinical trials, but epidemiologic outcomes and other research may be supported as well.

3. DRCR Retina Network Evolution 2003 - 202341 Multicenter Studies124 Publications 137 Active Clinical Studies2017Expansion to All Retinal Disease 2002DRCR.netCreated

4. Collaborative Network

5. Collaborative Network

6. Network Participation

7. FundingSponsored cooperative agreement initiated September 2002Current award 2019-2023Grant application submitted in May 2022 for 2024-2028

8. Priority InitiativesInvolvement of community-based practices, as well as “academic” or university-based centers. Collaborate with industry to facilitate investigations and pursue opportunities otherwise not possible and to do so in a manner consistent with the Network’s dedication to academic integrity and optimal clinical trial performance.

9. Number of Active Sites by Location9

10. Number of Participants by Location10

11. How to Join the NetworkAll retina specialists in the U.S. and Canada are welcome to applyE-mail drcrnet@jaeb.orgYour request will be reviewed and if approved the necessary paperwork will be sent to you

12. Access to Publications and PresentationsPublications and Presentations can be found on the public website12

13. How to Submit a Protocol IdeaProtocol Idea Forms are available on the public website under Home  Information about the NetworkE-mail form to drcrnet@jaeb.orgIdeas will be reviewed by the applicable Steering Committee as they are submitted

14. Protocol Idea Review ProcessSC=Steering CommitteeEC= Executive CommitteePDC = Protocol Development Committee

15. Current Protocols

16. Upcoming StudiesA Randomized Clinical Trial Evaluating Intravitreal Faricimab (6.0 mg) vs Injections or Fluocinolone Acetonide (0.19 mg) Intravitreal Implants vs Observations for Prevention of Visual Acuity Loss due to Radiation Retinopathy – Protocol ALHome OCT-Guided Treatment versus Treat and Extend for the Management of Neovascular AMD – Protocol AO16

17. Upcoming Studies and Site InterestProtocol AL10-15 brand new sites to join25-30 total sites expectedExpected to start certification October 2023Protocol AO80 Sites expected to participateExpected to start certification October 202317

18. DRCR Major Findings18Two Decades of Revolutionizing Diabetic Retinopathy Care: Diabetic Macular Edema 2008Protocol B: Laser superior to corticosteroid for DME2010Protocol I: Anti-VEGF superior to laser for DME2015Protocol T On average, aflibercept outperforms other anti-VEGF agents for DME at one year when starting with moderate or worse vision lossOn average, bevacizumab and ranibizumab 0.3-mg perform similarly to aflibercept at 1 year when starting with mild vision loss

19. DRCR Major Findings19Two Decades of Revolutionizing Diabetic Retinopathy Care: Diabetic Macular Edema 2018Protocol U: Dexamethasone + ranibizumab does not improve VA at 6 months compared with ranibizumab alone for eyes with persistent DME following anti-VEGF therapy2019Protocol V: Among eyes with CI-DME and good visual acuity (20/25 or better), VA loss after 2 years was similar regardless of whether initial management was aflibercept, laser, or observation2022Protocol AE: Photobiomodulation as given in this study, while safe and well tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision. Protocol AC: No evidence of a significant difference in visual outcomes over a 2-year period between aflibercept monotherapy and treatment with bevacizumab first with a switch to aflibercept in the case of suboptimal response

20. DRCR Major Findings20Two Decades of Revolutionizing Diabetic Retinopathy Care: Diabetic Retinopathy 2018Protocol S: Mean change in VA with ranibizumab similar to PRP at 5 years2015Protocol S: Anti-VEGF at least as good as PRP for PDR for VA at 2 years2020Protocol AB: In eyes with VH from PDR, vision improved more quickly with vitrectomy compared with aflibercept but there was no significant difference in mean VA letter score over 24 weeks.

21. DRCR Major Findings21Two Decades of Revolutionizing Diabetic Retinopathy Care: Diabetic Retinopathy 2021Protocol W (2-Year): Among eyes with moderately severe to severe NPDR, the proportion that developed PDR or CI-DME was lower with periodic aflibercept treatment compared with sham but did not result in VA benefit through at least 2 years.2022Protocol W (4-Year): Preventative aflibercept treatment compared to sham in eyes with moderate to severe NPDR (DRSS level 34-53) and VA 20/25 or better (≥ 79 letters) Lowered the probability of developing PDR or CI-DME within 4 yearsDid not confer VA benefit at 4 years

22. DRCR Major Findings22Other Retinal Diseases2021Protocols AG and AH: In most eyes with VMT, PVL induced hyaloid release. In eyes with macular hole, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears.

23. Recently Completed Protocols

24. Protocol AAPeripheral DR Lesions on UWF Fundus Images and Risk of DR Worsening Over Time

25. Study RationaleIf peripheral DR lesions improve our ability to predict DR worsening or improvement, this could:Change patient management, evaluation and follow-upGive new insights into mechanisms for changes in retinal pathologyAllow fewer images leading to faster imaging time and greater patient comfortIf peripheral DR lesions are not shown to improve this ability, then such imaging may not be needed in the management of DR

26. Eligibility Criteria:At least one eye with NPDR and without CI-DMEAnnual Visits for 4 YearsStudy DesignProspective, Observational Longitudinal Study26Treatment for any indication is at investigator discretion

27. ObjectiveAssess whether presence of predominantly peripheral lesions (PPL) on UWF images is associated with rates of DR worsening over timePPL defined as DR lesions located primarily outside versus within the 7 standard ETDRS fields for any field of the retinal peripheryPPL graded on UWF color photographs (Color-PPL) and on UWF FA (FA-PPL)27

28. Primary OutcomeProportion of eyes experiencing DR worsening by 2 or more steps from baseline and/or receipt of DR treatment through 4 yearsOutcome assessed within the ETDRS fields on UWF color photosEyes receiving treatment with anti-VEGF, steroid, or vitrectomy for conditions other than DR (including DME) were censored 28

29. Summary ResultsIn this cohort:Risk of DRSS worsening or treatment was not associated with Color-PPL but was significantly associated with FA-PPL, when adjusting for baseline DRSS level. Eyes with FA-PPL had a 1.7-fold greater risk of disease worsening over 4 years. This association was consistently present within DRSS subgroupsMultiple PPL lesion types (H/Ma and IRMA) were individually associated with DRSS worsening or treatmentThus, among eyes with NPDR, the presence of PPL identified using UWF-FA imaging appears to be a marker for increased risk of disease worsening that is not detectable using standard ETDRS 7-field photography or UWF-color imaging alone. 29

30. ConclusionsAlthough no association was identified with color-PPL, the presence of FA-PPL was associated with a significantly greater risk of ETDRS-DRSS worsening or treatment over 4 years independent of DRSS level. These results suggest use of UWF-FA to evaluate retina peripheral to standard ETDRS fields improves the ability to predict disease worsening in NPDR eyes. These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes.

31. Secondary ObjectiveTo evaluate the association of retinal nonperfusion (NP) on UWF fluorescein angiography (FA) with diabetic retinopathy (DR) severity and predominantly peripheral lesions (PPL) at baseline.31

32. Outcomes MeasuredDRSS level evaluated within ETDRS fields on UWF-Color imagesPPL graded for each extended ETDRS field on UWF-color images and on UWF-FADefined as DR lesions located primarily outside versus within the 7 standard ETDRS fields for any field of the retinal peripheryUWF-FA images were also evaluated for:Total gradable area (mm2)Extent of retinal nonperfusion (mm2)Nonperfusion index (NPI; ratio of nonperfused to total gradable area)

33. Summary ResultsWorse DRSS severity was strongly associated with increases in nonperfusion.Nonperfusion identified on UWF-FA in these diabetic eyes was located primarily in the mid- and far- periphery that are not visualized by standard ETDRS FA imaging. No significant association between overall nonperfusion and presence of color-PPL was identified.FA-PPL has been shown to be associated with increasing nonperfusion that co-localizes with the retinal areas of nonperfusion. 33

34. DiscussionThe baseline association between both peripheral and posterior pole nonperfusion with increasing DR severity supports continued evaluation of nonperfusion on UWF-FA as a possible prognostic marker of DRSS worsening in this study. One possible explanation for the discrepancy between color-PPL and FA-PPL associations with nonperfusion may be due to the fact that UWF-FA detects significantly more DR lesions as compared to UWF-color imaging.Evaluation of nonperfusion in the mid and far retinal periphery may be important in understanding disease evolution in eyes with diabetic retinopathy.34

35. Protocol AKHome OCT Monitoring System: Feasibility Study

36. BackgroundTreatment of neovascular AMD (nAMD) with anti-VEGF therapy is a major improvement but at a very high treatment burden and cost for patients and the healthcare systemThe ability to perform daily monitoring of intraretinal fluid and subretinal fluid using a home optical coherence tomography (OCT) system offers the opportunity to obtain a detailed assessment of fluid over timeUnderstanding fluid dynamics for an individual patient may allow customization of treatment that may reduce treatment burden and improve long-term outcomes36

37. Notal Vision Home OCTNotal Vision has developed an OCT system for at-home use, called Home OCT systemThe Notal Home OCT is an investigational device not cleared for clinical usePatient self-images daily Process takes less than one minute per eyeDense 88 B-scans spaced 30 µm in 3x3 mm field of view visualizes small amounts of fluidAutomatic data transmission to cloud 37

38. Notal Vision Home OCTMonitoring center performs AI based quantification and tracking of intra- and subretinal fluid volumeRetina specialist sets fluid volume thresholds and is notified by monitoring center when criteria are methas 24/7 access to all images and databills for data review every 30 days 38Home OCT ImageHome OCT Device

39. Critical Questions for Home OCTCan the use of Home OCT monitoring reduce visit and treatment burden and at least maintain or possibly improve VA outcomes?Need large RCT to determine its role in clinical practiceNo such trial currently planned – will be FDA approved as a device with no efficacy trial requiredWhat amount of recurrent fluid should be used as a threshold to prompt a follow up visit with a retina specialist?Will AI be sufficient for screening for recurrent activity?Logistics and how would interface with DRCR Retina Network not well understoodNeed feasibility study39

40. Protocol AK: Home OCT Feasibility StudyInclusion Criteria:Best corrected E-ETDRS VA 20/20 to 20/320Ability to take daily Home OCT scansActive choroidal neovascularization (CNV) due to AMD in at least one eye in which the investigator intends to treat with anti-VEGFAMD defined as presence of at least one large drusen in either eyeActive CNV defined as presence of intraretinal or subretinal fluidExclusion Criteria:History of CNV or treatment for CNV in the study eyeParticipants will take daily Home OCT scans for 6 monthsFollow-up visits will occur as normally seen with standard careAny OCT scans obtained on the study eye (none are mandated by the study) will be uploaded to the Coordinating Center for grading & comparison with Home OCT scan taken same dayObservational Study of 10 participants from 3 sites

41. What We Will LearnMethods and logistics of image/data interpretation and transfer from NotalWillingness of patients to participate in and complete a program requiring home OCT monitoringAbility of clinic and Notal staff to educate patientBetter understand fluid dynamics associated with treatmentAgreement between Reading Center assessment of fluid on in-office OCT versus NOA fluid determinations from Home OCT scans 41

42. The primary manuscript has been submitted for publication. Results will be shared soon!42

43. Recruiting Studies43

44. Protocol AFA Randomized Trial Evaluating Fenofibrate for Prevention of Diabetic Retinopathy Worsening

45. Study RationaleWidespread use of an oral agent, fenofibrate, that is effective at reducing worsening of DR might decrease the numbers of patients who develop vision-threatening complications and need to undergo invasive treatmentReduce vision loss from advanced DRReduce complications/adverse events associated with invasive and expensive treatmentsLong term study will provide opportunities to evaluate new imaging, visual function tests, methods for DR detection45

46. History of FenofibrateTwo placebo-controlled clinical trials (FIELD and ACCORD) demonstrated a beneficial effect of fenofibrate on diabetic retinopathy as part of pre-planned secondary analysesHowever, for various reasons, treatment with fenofibrate has not been adopted by retina or systemic care practitionerslack of information belief that data is not strong enough to change practice hesitation to use a systemic drug by ophthalmologistsinability to successfully grade retinal disease by PCPs46

47. DRCR Retina Network Study ObjectivesTo determine if fenofibrate is effective at preventing DR worsening in participants with mild to moderate non-proliferative DR and no CI-DME at baseline through 4 years of follow-upIf effective, additional goals of the study areTo provide a model for ophthalmologists to prescribe and/or collaborate with an internist to prescribe and monitor the drug safely Disseminate standardized prescribing guidelines with the aim to encourage broader useCollect information on potential predictive biomarkers via blood sampling, functional and structural testing as well as glucose level from CGM over course of DR progression.47

48. Ancillary Ocular ComponentsData from visual function assessments such as contrast sensitivity, visual field (VF) testing and structural data from OCT angiography (OCTA) will provide valuable info on potential predictive biomarkers of functional outcomes over natural history of DR progressionSpecific objectives include:Quantification of VF and contrast sensitivity at baseline & evaluation of relationship with DR severity levelIdentification of biomarkers on OCTA at baseline that are associated with retinopathy progressionExplore whether fenofibrate treatment has any effect on VF and/or contrast sensitivity48

49. Contrast SensitivityContrast sensitivity will be assessed using Adaptive Sensory Technology (AST) platformContrast sensitivity is measured using an iPad like device, which will obtain the full contrast sensitivity curve across a spectrum of spatial frequencies30 devices will be available for placement at select sitesTraining will be provided by AST49

50. Continuous Glucose Monitoring (CGM)Primary objective of the CGM sub-study is to evaluate the relationship between glycemic parameters (e.g., time in range) with DR progression Preliminary data from DCCT fingerstick samples suggests an association between TIR and development or progression of DR (Beck, et al)Participants in this study will wear a CGM following each 6M visit to provide prospective, longitudinal CGM data in a large cohort at risk of DR progression50

51. Study Design51Major Patient-level criteria:No contraindication to fenofibrate use, no severe renal disease, no liver disease (defined via central lab values)No prior treatment for DME or DR No anticipated need for intravitreous anti-VEGF or PRP in the next 6 months No history of intravitreous anti-VEGF or corticosteroid treatment within the prior yearEye-level criteria (according to the investigator, confirmed by RC grading):Either (1) both eyes have ETDRS DR severity level between 35 and 47 (mild NPDR to moderately severe NPDR) or (2) one eye has mild to moderately severe NPDR and the other has microaneurysms only (DR severity level 20).Both eyes must have best-corrected E-ETDRS VA letter score ≥79 Both eyes must not have CI-DME (using standard DRCR OCT thresholds)Multi-Center Randomized Clinical Trial (N = 910)Primary Outcome: Proportion of eyes with DR worsening by 4 years160 mg FenofibratePlacebo

52. Protocol AJVitreous Proteomics in Eyes with a Macular Hole

53. Study Rationale53There is an ongoing need to better understand key molecular pathways in the pathogenesis of retinal diseases. Elucidation of proteins involved in these pathways could:Improve our scientific understandingIdentify novel targets for more effective treatmentEnhance our ability to predict disease course or response to currently available treatmentsVitreous is a potentially rich source of proteins that may directly reflect biochemical processes that are active in or influence the retina.

54. BackgroundZhang et al. (Clin Proteomics 2017) conducted a discovery phase study of the vitreous proteome in 4 patients with macular holes and 6 controls (patients with dropped IOL):5912 vitreous proteins found32 had increased and 39 had decreased expression in eyes with macular holes compared with controls.  The proteomic analysis from this small discovery phase study revealed proteins and biological pathways that could be targeted in future studies.54

55. Study Objective55Verify and characterize abnormally expressed vitreous proteins in adults with full thickness macular holes (MH).Identify pathways involved in the pathogenesis of macular hole formation to determine potential targets for therapeutic intervention.

56. Study Design56Adults with 1 eye that meets all of the eligibility criteria:Planned standard-of-care vitrectomy to repair full-thickness macular hole, remove visually significant floaters or to retrieve dislocated or subluxated IOLEligibility will be confirmed on OCT by a central reading centerSample Collection Repository(160 Eyes; 60 in discovery phase, 100 in validation phase)Validation Phase Processing and AnalysesDiscovery Phase Processing and AnalysesSample collection during standard-of-care vitrectomy

57. Discovery Phase57Sample size: 60 eyes30 eyes with MH30 eyes with visually significant floatersDetermine which proteins are up- and down-regulated in the vitreous of eyes with MH. Processing and analyses include:Tandem mass tag (TMT) labelingProcessing the samples and analyzing with mass spectrometryBioinformaticsPreliminary results are being reviewed

58. Validation Phase58Sample size: 100 eyes50 eyes with MH50 control eyes (control to be determined based on discovery phase results)Target the most promising proteins found in the discovery phase Processing and analyses include:Selective reaction monitoring (SRM) using labeled peptidesProcessing the samplesBioinformatics

59. Protocol AMRandomized Trial Comparing Immediate vs Deferred Surgery for Symptomatic ERMs

60. RationaleVitrectomy with ERM peeling has a high success rate, yet some patients experience less than optimal VA improvementPatients with significant macular changes on OCT but relatively good vision advised to defer surgery until vision declines to 20/40 or worse60

61. RationaleIt is unknown whether delaying surgery, which allows the foveal architecture to remain compromised and potentially to deteriorate, results in worse VA outcomes than if surgery is performed earlierThere is a need to better understand predictors of outcomes when surgery is performed and predictors of progression when surgery is deferred61

62. Study ObjectivesCompare:Change in VA (primary)Changes in visual function, reading speed, OCT outcomesComplication ratesDeferred groupDetermine the rate of and time to progression of ERM to needing vitrectomyAssess risk factors for progression62

63. Study DesignAt least 1 eye meeting all the following criteriaE-ETDRS visual acuity 20/25 to 20/40 (69 to 83 letters)ERM must be thought to be the primary cause of vision lossERM meeting the following criteria (no RC confirmation required)Symptoms of visual loss and/or distortion (and in the opinion of the investigator, the ERM is contributing to the participant’s symptoms); either new or worsening in the past 24 monthsEpiretinal membrane involving or altering the central 3 mm of the macula on OCT Distortion within the central subfield by ERM on OCT Multi-Center Randomized Clinical Trial (400 Eyes)Primary Outcome: Mean change in visual acuity letter score from baseline to 36 months63Immediate Surgery (within 4 weeks)Deferred Surgery (vitrectomy only if protocol criteria met)

64. Study Design64

65. Protocol ANA Phase 2 Evaluation of Tonabersat for Diabetic Macular Edema

66. Phase 2 Study Objective 66Assess the effects of orally available tonabersat on central subfield thickness (CST) compared to placebo in eyes with center-involved DME (CI-DME) and good visual acuity

67. Phase 2 trial will determine whether a phase 3 trial has merit Short duration: 12 months67Protocol AN: Tonabersat for DME

68. Study RationaleCurrent DME treatments are costly, invasive and can require frequent visitsAn effective, well-tolerated, low-cost, and non-invasive treatment for DME would reduce patient burden by:reducing costsreducing frequency of treatment visitsdelay or avoid injections or other invasive treatments68

69. Tonabersat Background69Orally availableDosed once daily (two pills, 80mg total)Targets connexin43 hemichannels that are overexpressed in DR, reducing the activation and recycling of proinflammatory cytokinesInitially developed for treatment of migraine

70. Study Design70Inclusion:Adults with type 1 or 2 DMBest corrected E-ETDRS VA letter score ≥ 79 CI-DME confirmed by CST on OCTExclusion: Chronic renal failure requiring dialysis or kidney transplantModerate to severe hepatic impairmentAnticipated need to treat DME or DR in first 6 monthsMajor ocular surgery in past 4 monthsTreatment for DME or DR in past yearMulti-Center Randomized Clinical Trial (128 Participants)Primary Outcome: Mean change in CST at 6 monthsPlacebo(two pills)80mg qdTonabersat(two pills)

71. Follow-up71Months 1 & 3 VisitsBCVAOCTEye ExamBlood PressureOn-site preg testSafety AssessmentDrug ComplianceUrine sample Blood sampleMonth 12 VisitBCVAOCTEye ExamBlood PressureOn-site preg testSafety AssessmentUrine sample Blood sampleMonths 2, 4 & 5 VisitsBCVAOCTEye ExamBlood PressureOn-site preg testSafety AssessmentDrug Compliance*OCTA at select sites, only in the study eye(s)Month 6 VisitBCVAOCTEye ExamBlood PressureOn-site preg testSafety AssessmentDrug ComplianceUrine sample Blood sampleFundus photosOCTA*Additional biomarker labs (dry ice needed)PRIMARY OUTCOME STOP STUDY DRUG

72. Protocol AQLabcorp Recruitment Demonstration Project

73. BackgroundDiabetes Mellitus: fastest growing chronic disease worldwideDiabetic Retinopathy: a leading cause of acquired blindness in the Western world9.60 million Americans affected 27% of US adults 40 and older affectedHigher prevalence among Black (34%) and Hispanic (29%)DRCR is interested in identifying new sources of potentially eligible patients for studies in diabetic retinopathy and other retinal diseases73

74. Study RationaleRecruitment challenges for clinical trial participants with early diabetic eye disease, particularly when vision is good (AF and AN)Explore and evaluate the identification of candidates for DRCR clinical trials using results from Labcorp laboratory tests and AST contrast sensitivity testing74

75. Secondary: evaluate the role of contrast sensitivity testing in selecting high-risk patientsGoal to facilitate and increase recruitment for DRCR diabetes-related eye diseases studies Objectives75PrimaryEvaluate the identification of clinical trial candidates by using results from Labcorp laboratory tests

76. Eligibility CriteriaLabcorp EmailDiagnosed with diabetesICD-10 diagnosis codes: E11 and all subcodesBetween 18 and 80 years Contact allowed via Labcorp provisionsHbA1c/eGFR criteria met for high-risk of DR or DMELocated ≤ 25 miles of selected DRCR sitesDRCR CallHbA1C level ≥ 8%Diabetes duration of 10 to 14 years (obtained via survey)OR, eGFR 15 mL/min to 59 mL/minOR, Duration 15 or more years (obtained via survey)76

77. Study Design77

78. In-Clinic TestingParticipantDemographic informationMedical historyPhysical examinationEyes (Bilateral)Electronic-ETDRS VAAST contrast sensitivityColor fundus photographsSpectral-domain OCTOcular examination Dilated eye examination 78

79. ROP Studies – Collaboration with PEDIG

80. ROP4 Study QuestionsPrimary study question: For eyes with type 1 ROP in zone I, what is the short-term effectiveness of 0.063 mg and 0.25mg?Secondary questions:What are refractive outcomes?What is the extent of retinal vascularization?

81. DesignRCT, with 1:1 randomization to:0.063 mg bevacizumab0.25 mg bevacizumab

82. ROP4 Update33 subjects enrolled so far towards goal of 8023 Sites, 3 pending certification Protocol amendment to add 2-year Bayley IV Neurological Testing and Ocular Exam

83. GeneticsGenes in Diabetic Retinopathy Project83

84. Genes in Diabetic Retinopathy ProjectObjectiveTo create a repository of genetic material and clinical phenotype information as a resource for the research community The database may provide the opportunity to assess genetic susceptibility and resistance to DR and also variants impacting visually-important biomarkers for ME and neovascularizationMajor Eligibility CriteriaPrevious/current participant in a DRCR Retina Network studyEnrollment (Ongoing)Total enrolled: 2,739 subjects (as of 5/19/23)84

85. DRCR Retina Network Role in AI Efforts for Retinal Disease85

86. DRCR Retina Network Role in AI Efforts for Retinal DiseaseMultiple groups currently working on detection algorithms for DR, AMD, and other retinal diseaseThe Network is uniquely poised to contribute to these effortsHigh quality imagesRigorous phenotyping of study participantsLongitudinal datasetsOutcomes addressing treatment responseCollective expertise in diagnosis and management of retinal disease86

87. DRCR Retina Collaborations in AIThe Network is interested in collaborating with groups with active AI efforts Detecting retinal disease Identifying risk of worsening Predicting treatment responseCollaborators may be academic or industry partnersAI/Deep Learning Proposal Idea Form available on the Public WebsiteMajor goals:Encourage widespread use of DRCR Retina Network images/dataMeaningful Network participation in interpreting and reporting results87

88. DRCR Retina NetworkThank you88