You are here: » Vision Research » Visionary of the Quarter » Anat Loewenstein (Q01-2022)

The research work of Professor Anat Loewenstein

Professor Anat Loewenstein

Professor Loewenstein's main field of research is the investigation of drug administration and toxicity to the retina, early detection of age macular degeneration (AMD) and home monitoring of neovascular age related macular degeneration (n-AMD). Prof. Loewenstein's research is focused on the clinical technological development of early detection and treatment of this condition through novel technologies and initiatives, evolving cooperation with pharmaceutical and biotech companies. Additionally, Prof. Loewenstein's goal is the clinical development of ground breaking technologies, such as, the implementation of augmented reality/ virtual reality and artificial intelligence and deep learning algorithms into the medical field in general, and specifically into routine clinical ophthalmological practice and vitreoretinal surgeries.

Remote patient monitoring with self-operated OCT for n-AMD management

The present treatment for exudative age related macular degeneration entails many challenges, including timely detection and retreatment decisions based on  frequent follow-up visits to the retinal clinic. The current model of care is suboptimal and leads to severe visual deterioration due to the burden of recurring visits and to discontinued treatment as a result. Moreover, clinicians are required to base their treatment decisions on a single OCT scan at a singular moment in time and to compare it, usually, to a previous OCT scan from the previous month. This limitation can lead to suboptimal visual outcomes and to a further visual decline. Furthermore, the assessment of the patient's disease status is not accurate enough and usually is limited to an estimate of retinal fluid status. Precise quantification of retinal fluids and evaluation of temporal fluid volume dynamics are required. All of these challenges can be overcome via remote patient monitoring with self-operated home OCT, implementing artificial intelligence algorithm, which in turn, interprets the enormous data received from the scans provided by the home OCT device. Such a device already exists and was tested successfully in several studies, including prospective randomized controlled trials and real world studies. The analysis of fluid trajectories enables a distinct and individualized alert threshold, set by the treating physician, which in turn, will be identified by the home OCT monitoring service providers. Any change in location or in the quantity of retinal fluids will set an alert and facilitate a fully informed and personal clinical treatment. Different biomarkers are implemented within the artificial algorithm and are taken into consideration, including, the slope of volume increase and decrease, minimum and maximum fluid volume between intravitreal injections, etc. It should be noted that in a recent real world study examining the performance of the home OCT device two remarkable findings were obtained: 94% of the study population with mean age of 74 managed to obtain gradable imaging. Also, there was an exceptionally high level of agreement between human graders and the home OCT device on fluid status - 94.7%.

All of the mentioned biomarkers can contribute to necessary and informed treatment modifications, for example, a quicker shift from from off- to on-label medication or perhaps, a switch to a longer acting drug. In addition, treatment intervals may be extended and alleviate patients' burden due to the numerous visits required nowadays, in order to properly monitor a chronic condition, such as, n-AMD. This modality can be implemented in the real world only if the following steps will be implemented: conduction of multi-centered clinical trials, comparing treatment outcomes with and without automated quantification. Additionally, FDA approval, implementation of the AI software into the OCT device, widespread awareness to the potential benefits of AI in clinical practice and a full cooperation between home OCT monitoring providers and the treating clinicians.

Figure 1 illustrates potential key biomarkers in the monitoring of n-AMD. This bilateral n-AMD case demonstrates the difference in treatment response between the eyes of an 85-year-old patient treated with intravitreal injection on a treat-and-extend regime. The figure shows that the area under the curve, depicting the cumulative retinal fluid volume, during a single treatment cycle can vary remarkably between two eyes of the same patient, despite very similar OCT scans during the visit to the retinal clinic.

Figure 1: Intraretinal fluid (IRF) and subretinal fluid (SRF) volume trajectories from Notal OCT Analyzer (NOA) segmentation of daily home OCT self-images of a patients' right and left eye.

Augmented Reality Video Microscope for vitreoretinal surgery as a replacement for the operational Microscope

Beyeonics Surgical Ltd. has been utilizing the Augmented Reality Video Microscope (ARVM) for enhancing visualization of combat and commercial pilots during their flights. Recently, this device has been applied and implemented into vitreoretinal surgery.

The Beyeonics One system is focused around an imaging unit equipped with 3D stereoscopic cameras. The headset is controlled by head gestures and a footswitch. Surgeons can use these to constantly change their point of view in the operating room.

During surgery, high-resolution video from those cameras is transferred to a screen, an optional external display, (with the assistance of novel virtual reality and artificial intelligence methods) and a head-mounted monitor that provides an up-close view through the microscope. This device has the capability to meet the visual, informational, and ergonomic needs of the surgeon during different stages of the surgery. In a recent study conducted in Tel-Aviv Medical Center, the ARVM was utilized and tested for imaging quality, its effect on surgical outcomes and for facilitating improved decision making during surgery. During a pre-scheduled vitrectomy, a few parameters were examined in order to measure the following parameters: surgical performance, ergonomics and setup time. Also, the OCT data was demonstrated in real time during surgery with response to retinal visualization, received from the ARVM. Remarkable retinal visualization was achieved with successful extraction of silicone oil from the vitreous cavity: manipulation of digital images enabled control of image rotation, light parameters, digital zooming and image enhancement. Additionally, setup time was short and the adjustment to the head monitor was also easy. The head monitor did not cause any stress or fatigue to the operating surgeon and it was extremely comfortable. Moreover, it allowed for a direct video projection through the whole surgical procedure.

Figure 2: Augmented Reality Video Microscope in the OR

Key Publications

  1. Loewenstein A, Ferencz JR, Lang Y, Yeshurun I, Pollack A, Siegal R, Lifshitz T, Karp J, Roth D, Bronner G, Brown J, Mansour S, Friedman S, Michels M, Johnston R, Rapp M, Havilio M, Rafaeli O, Manor Y. Toward earlier detection of choroidal neovascularization secondary to age-related macular degeneration: multicenter evaluation of a preferential hyperacuity perimeter designed as a home device. Retina. 2010 Jul-Aug; 30(7):1058-64.
  2. Waisbourd M, Shemesh G, Top LB, Lazar M, Loewenstein A. Comparison of the transpalpebral tonometer TGDc-01 with Goldmann applanation tonometry. Eur J Ophthalmol. 2010 Sep-Oct; 20(5):902-6.
  3. Mezad-Koursh D, Zayit-Soudry S, Barak A, Loewenstein A. Unilateral Idiopathic Macular Telangiectasia with Choroidal Neovascularization. Ophthalmic Surg Lasers Imaging. 2010 Mar 9:1-3.
  4. Golan S, Shalev V, Goldstein M, Treister G, Chodick G, Loewenstein A. The rate of myocardial infarction events among patients with age-related macular degeneration: a population-based study. Graefes Arch Clin Exp Ophthalmol. 2011 Feb; 249(2):179-82.
  5. Zayit-Soudry S, Zemel E, Barak A, Perlman I, Loewenstein A. Safety of intravitreal bevacizumab in the developing rabbit retina. Retina. 2011 Oct; 31(9):1885-95.
  6. Golan S, Shalev V, Treister G, Chodick G, Loewenstein A. Reconsidering the connection between vitamin D levels and age-related macular degeneration. Eye (Lond). 2011 Sep; 25(9):1122-9.
  7. Barak A, Burgansky-Eliash Z, Barash H, Nelson DA, Grinvald A, Loewenstein A. The effect of intravitreal bevacizumab (Avastin) injection on retinal blood flow velocity in patients with choroidal neovascularization. Eur J Ophthalmol. 2012 May-Jun; 22(3):423-30.
  8. Shahar J, Zemel E, Perlman I, Loewenstein A. Physiological and toxicological effects of cefuroxime on the albino rabbit retina. Invest Ophthalmol Vis Sci. 2012 Feb 21; 53(2):906-14.
  9. Michaeli A, Soiberman U, Loewenstein A. Outcome of iris fixation of subluxated intraocular lenses. Graefes Arch Clin Exp Ophthalmol. 2012 Sep; 250(9):1327-32.
  10. Loewenstein A. Use of home device for early detection of neovascular age-related macular degeneration. Ophthalmic Res. 2012; 48 Suppl 1:11-5.
  11. Moisseiev E, Goldstein M, Waisbourd M, Barak A, Loewenstein A. Long-term evaluation of patients treated with dexamethasone intravitreal implant for macular edema due to retinal vein occlusion. Eye (Lond). 2013 Jan; 27(1):65-71.
  12. Fischer N, Moisseiev E, Waisbourd M, Goldstein M, Loewenstein A. A matched-control comparison of serious adverse events after intravitreal injections of bevacizumab for age-related macular degeneration and cataract extraction. Clin Ophthalmol. 2013; 7:621-5.
  13. Coscas G, Augustin A, Bandello F, de Smet MD, Lanzetta P, Staurenghi G, Parravano MC, Udaondo P, Moisseiev E, Soubrane G, Yatziv Y, Loewenstein A. Retreatment with Ozurdex for macular edema secondary to retinal vein occlusion. Eur J Ophthalmol. 2014 Jan-Feb; 24(1):1-9.
  14. Moisseiev E, Loewenstein A. Simulation of laser retinopexy around retinal breaks for ophthalmologists in training. Ophthalmologica. 2015; 233(1):51-5.
  15. Chakravarthy U, Goldenberg D, Young G, Havilio M, Rafaeli O, Benyamini G, Loewenstein A. Automated Identification of Lesion Activity in Neovascular Age-Related Macular Degeneration. Ophthalmology. 2016 Aug; 123(8):1731-1736.
  16. Giladi M, Edri I, Goldenberg M, Newman H, Strulovich R, Khananshvili D, Haitin Y, Loewenstein A. Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. Protein Expr Purif. 2017 Apr; 132:138-142.
  17. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, Berg K, Chakravarthy U, Gerendas BS, Jonas J, Larsen M, Tadayoni R, Loewenstein A. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017; 237(4):185-222.
  18. Bar-Sela SM, Zayit-Soudry S, Massarweh A, Mane I, Perlman I, Loewenstein A. Retinal Toxicity in Albino Rabbits. J Clin Exp Ophthalmol. 2018; 9(1) :707.
  19. Zur D, Iglicki M, Busch C, Invernizzi A, Mariussi M, Loewenstein A; International Retina Group. OCT Biomarkers as Functional Outcome Predictors in Diabetic Macular Edema Treated with Dexamethasone Implant. Ophthalmology. 2018 Feb; 125(2):267-275.
  20. Iglicki M, Busch C, Zur D, Okada M, Mariussi M, Chhablani JK, Cebeci Z, Fraser-Bell S, Chaikitmongkol V, Couturier A, Giancipoli E, Lupidi M, Rodríguez-Valdés PJ, Rehak M, Fung AT, Goldstein M, Loewenstein A. DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study. Retina. 2019 Jan; 39(1):44-51.
  21. Iglicki M, Zur D, Busch C, Okada M, Loewenstein A. Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'. Acta Diabetol. 2018 Jun; 55(6):541-547.
  22. Iglicki M, Zur D, Fung A, Gabrielle PH, Lupidi M, Santos R, Busch C, Rehak M, Cebeci Z, Charles M, Masarwa D, Schwarz S, Barak A, Loewenstein A; International Retina Group (IRG). TRActional DIabetic reTInal detachment surgery with co-adjuvant intravitreal dexamethasONe implant: the TRADITION STUDY. Acta Diabetol. 2019 Oct; 56(10):1141-1147.
  23. Loewenstein A, Korobelnik JF, Okada AA. A Patient with Type 1 Diabetes, Visual Acuity Loss, and Retinal Thickening. JAMA Ophthalmol. 2019 Sep 1; 137(9):1078-1079.
  24. Zur D, Iglicki M, Sala-Puigdollers A, Chhablani J, Lupidi M, Fraser-Bell S, Mendes TS, Chaikitmongkol V, Cebeci Z, Dollberg D, Busch C, Invernizzi A, Habot-Wilner Z, Loewenstein A; International Retina Group (IRG). Disorganization of retinal inner layers as a biomarker in patients with diabetic macular oedema treated with dexamethasone implant. Acta Ophthalmol. 2020 Mar; 98(2):e217-e223.
  25. Rosenblatt A, Udaondo P, Cunha-Vaz J, Sivaprasad S, Bandello F, Lanzetta P, Kodjikian L, Goldstein M, Habot-Wilner Z, Loewenstein A; ARTES Study Group. A Collaborative Retrospective Study on the Efficacy and Safety of Intravitreal Dexamethasone Implant (Ozurdex) in Patients with Diabetic Macular Edema: The European DME Registry Study. Ophthalmology. 2020 Mar; 127(3):377-393.
  26. Sharma A, Kuppermann BD, Bandello F, Lanzetta P, Zur D, Park SW, Yu HG, Saravanan VR, Zacharias LC, Barreira AK, Iglicki M, Miassi F, Veritti D, Tsao S, Makam D, Jain N, Loewenstein A. Intraocular pressure (IOP) after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations-GEODEX-IOP study. Eye (Lond). 2020 Jun; 34(6):1063-1068.
  27. Okada M, Wong TY, Mitchell P, Eldem B, Talks SJ, Aslam T, Daien V, Rodriguez FJ, Gale R, Barratt J, Finger RP, Loewenstein A. Defining Nonadherence and Nonpersistence to Anti-Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2021 Jul 1; 139(7):769-776.
  28. Sharma A, Kumar N, Parachuri N, Bandello F, Kuppermann BD, Loewenstein A. Ranibizumab Biosimilar (Razumab) vs Innovator Ranibizumab (Lucentis) in neovascular age-related macular degeneration (n-AMD)- efficacy and safety (BIRA study). Eye (Lond). 2021 Jun 22. doi: 10.1038/s41433-021-01616-9. Epub ahead of print.

Professor Anat Loewenstein, MD, MHA

Tel-Aviv Medical Center
Ophthalmology Division
Weizmann 6
Tel-Aviv 6423906

Phone: +97236925773
E-mail: anatl[at]