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Competing Interests: Competing interests: Ashish Sharma; Consultant- Intas, Lupin, Bayer, Allergan, Novartis. Peter K Kaiser; Aerie, Allegro, Allergan, Allgenesis, Alzheon, Annexon Biosciences, AsclepiX, Aviceda, Bayer, Bausch and Lomb, Biogen Idec, Bionic Vision Technologies, Boehringer Ingelheim, Carl Zeiss Meditec, Clearside Biomedical, DelSiTech, DTx Pharma, Duet Therapeutics, Eyevensys, Galecto Biotech, Galimedix, Gemini Therapeutics, Glaukos, Innovent, iRenix, Iveric Bio, jCyte, Kanaph Therapeutics, Kanghong, Kodiak, LensGen, NGM Biopharmaceuticals, Inc., Novartis, Ocugenix, Oculis, Ocuphire, OcuTerra Therapeutics Inc., Omeros, Opthea, Oxurion, Palatin, Regeneron, RegenxBio, Retinal Sciences, Retrope, Roivant, Samsung Bioepis, Sandoz, Santen, Stealth Biotherapeutics, Sustained Nano Systems, Takeda, Théa, Ramin Tadayoni; AbbVie Allergan, Alcon, Apellis, Bayer, Boehringer Ingelheim, Genentech, Iveric Bio, KHB, Novartis, Oculis, Roche, Thea, Zeiss. Frank G Holz-F.G. Holz reports research grants and personal fees from Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, Roche/Genentech, Geuder, Heidelberg Engineering, ivericBio, Pixium Vision, Novartis, Zeiss; personal fees from Alexion, Grayburg Vision, LinBioscience, Stealth BioTherapeutics, Aerie, Oxurion. Luke Nicholson Optos (research funding), Bayer (Speaker fees), Abbvie (Speaker fees, advisory board), Roche (Speaker fees, Heidelberg (Speaker fees)). Clara Vazquez-Alfageme None. Sobha Sivaprasad- Dr Sivaprasad reported receiving financial support from AbbVie, Amgen, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Phamaceuticals, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics. Dr Sivaprasad is Editor in Chief of Eye. Taku Wakabayashi; None. Se Joon Woo- Dr Woo reported serving as a consultant for Samsung Bioepis and Panolos Bioscience; being cofounder of Retimark; serving as an advisory board member of Novartis and Novelty Nobility; receiving grants and personal fees from Samsung Bioepis, Novartis, Novelty Nobility, Alteogen, Kookje, and Curacle; and receiving lecture fees from Novartis, Bayer, Allergan, AbbVie, Alcon, Taejoon, SCAI Therapeutics, and Alteogen. David Sarraf; Amgen, Bayer, Endogena Therapeutics, Genentech, Iveric Bio, Novartis and Optovue/Visionix and receives research grants from Amgen, Boehringer, Genentech, Heidelberg, Optovue/Visionix, Regeneron, and Topcon. Nilesh Kumar; Lupin and Intas. Nikulaa Parachuri-None. Carl D Regillo-Adverum, Allergan, Annexon, Bausch and Lomb, Clearside, Eyepoint, Genentech/Roche, Iveric, Novartis, Kodiak, Notal, Merck, Ocular therapeutics, Regenxbio, Stealth, Takeda, Zeiss and receives research support from Adverum, Allergan, Annexon, Eyepoint, Genentech/Roche, Novartis, Kodiak, Iveric, Regenxbio, Regeneron. Kourous A Rezaei- Consultant for Alcon Laboratories. Arshad M Khanani- Consultant: Adverum, Aerpio, Alimera, Allergan, Apellis, Asclepix, Aviceda, Bausch and Lomb, Broadwing Bio, Chengdu Kanghong, Cholgene, 4DMT, Dutch Ophthalmic Research Center, Gemini, Genentech, Glaukos, Graybug, Gyroscope, Iveric Bio, Janssen, Kato Pharma, Kodiak, Oculis, Opthea, Oxurion, Novartis, Polyphotonix, Recens Medical, Regeneron, Retrotope, Regenxbio, Roche, Surrozen, Thea, Unity Bio Research Support: Adverum, Apellis, Asclepix, Chengdu Kanghong, 4DMT, Gemini, Genentech, Graybug Vision, Gyroscope, Iveric Bio, Kodiak, Neurotech, NGM Bio, Ocular Therapeutix, Oculis, Opthea, Oxurion, Novartis, Recens Medical, Regenxbio, Roche, Unity Bio Equity: Aviceda, Gyroscope, Recens Medical, Retrotope, PolyphotonixSpeaker: Allergan, Genentech, Novartis. Francesco Bandello; CONSULTANT: Allergan, Bayer, Boehringer- Ingelheim, FidiaSooft, Hofmann La Roche, Novartis, NTC Pharma, Sifi, Thrombogenics, Zeiss. Mahesh Shanamugam; None. Lalit Verma; Consultant to Novartis, Bayer, Intas. Mangat Ram Dogra; None. NS Muralidhar; None. Manisha Agarwal; None. Anat Loewenstein; CONSULTANT: Allergan, Novartis, Roche, Notal Vision, Fiorsightslabs, Beyeonics, Bayer Health Care. Baruch D Kuppermann CLINICAL RESEARCH: Alcon, Alimera, Allegro, Allergan, Apellis, Clearside, Genentech, GSK, Ionis, jCyte, Novartis, Regeneron, ThromboGenics; CONSULTANT: Alimera, Allegro, Allergan, Cell Care, Dose, Eyedaptic, Galimedix, Genentech, Glaukos, Interface Biologics, jCyte, Novartis, Ophthotech, Regeneron, Revana, Theravance Biopharma, Dr Kuppermann acknowledges an unrestricted grant from Research to Prevent Blindness to the Gavin Herbert Eye Institute at the University of California, Irvine.

Aims: To report, using ultra-widefield angiography (UWFA) the area, distribution, and change in retinal capillary nonperfusion (RCNP) at baseline and 100 weeks in eyes with central retinal vein occlusion (CRVO) receiving anti-VEGF for macula oedema., Methods: Prospective longitudinal multi-centre cohort study. Adults with CRVO treated with anti-VEGF therapy for macular oedema underwent UWFA at baseline and week-100. The area, distribution, and change in total, peripheral and posterior pole RCNP were determined., Results: Of 153 eyes at baseline, mean area of RCNP was 34.3DA and 12 (7.8%) had ≥75DA RCNP. More than 10DA RCNP was present in the temporal periphery in 75.8% of eyes vs. 10.5% in the nasal periphery. At week-100, mean RCNP was 42.1DA with a median change from baseline of 3.3DA 95% CI [0.4, 7.3]; p < 0.01. Of 146 eyes with ≤10DA of posterior pole RCNP at baseline, 16/146 (11.0%) progressed to >10DA at week-100. These eyes had a median increase in total RCNP of 69.7DA [95% CI 27.2-85.4] vs 0DA [0.0-1.4]; p < 0.001 for those who did not, and two developed neovascular glaucoma. Larger baseline area of RCNP and history of glaucoma were risk factors for posterior pole RCNP developing., Conclusions: With UWFA, significant baseline RCNP was identified in the majority of CRVO patients, notably in the temporal periphery, but large increases over 100 weeks were uncommon. Development of >10DA posterior pole RCNP is a marker for widespread RCNP and in such cases the risk of anterior segment neovascularisation is not abolished by concomitant anti-VEGF therapy., (© 2021. The Author(s).)

PurposeIntraocular vascular endothelial growth factor (VEGF) levels increases with the severity of diabetic retinopathy. Response of diabetic macular oedema (DMO) to ranibizumab is driven by VEGF suppression. We hypothesised that the initial reduction of central macular thickness by ranibizumab should be maximum in severe diabetic retinopathy until the levels of VEGF decreases to the levels observed in eyes with mild retinopathy.MethodsConsecutive patients with centre-involving DMO (central subfield thickness (CSFT)>300 μm) who had three consecutive monthly ranibizumab injections followed by as needed therapy were included. Retinopathy status was graded as mild non-proliferative diabetic retinopathy (NPDR) (G1), moderate to severe NPDR with no prior panretinal photocoagulation (G2), and treated PDR (G3).ResultsTwo hundred and thirty-nine eyes from 204 patients with a mean age of 64.9 years were included. The distribution was 31.4 G1, 32.2 G2, and 36.4% G3. Mean baseline CSFT for all eyes was 458.5±110.8 μm. Baseline CSFT for G1, G2, and G3, respectively, were 437.6±90.9, 472.3±109.8, and 464.7±124.9 μm (P=0.2155). Mean change in CSFT after three consecutive injections was 128.5±116.6 μm. The mean changes were 95.8±101.4 μm for G1, 137.2±112.9 μm for G2, and 148.9±126.9 μm for G3. The changes in CSFT between groups adjusted for baseline CSFT were statistically significant (P=0.0473). At 6 and 12 months after a mean of 4.5 and 7.7 injections, the changes between groups were no longer significant, P=0.4783 and P=0.8271, respectively.ConclusionsThe initial anatomical response of DMO with intravitreal ranibizumab injections was maximum in eyes with treated PDR, suggesting that the higher the VEGF levels, the better the response with ranibizumab.