Gazing into the Future of Retina

by Joanna Lee Gazing into the Future of Retina

On C-test Scores

To clinically standardize an ordinal measure of monocular tritan discrimination, Dr. Ross Littlewood has developed the C-test 1 for blue and yellow contrast. The test consists of 10 novel pseudoisochromatic plates, each displaying a target with two blue/ yellow contrast borders and difficulty increasing from plates 1 to 10. The score is based on the last correctlyidentified plate.

The C-test is based on his observations of the koniocellular subsystem, which has several clinical benefits: It’s helpful in diagnosing amblyopia where only parvocellular signals are blocked, however, C-tests would show up as normal because koniocellular signals remain normal.

“This is useful where loss of vision occurs in someone without a welldocumented history,” said Dr. Littlewood. Another application is ascertaining retinal ischemia and edema. Ischemic situations (like advanced diabetic retinopathy) have a worse prognosis if tritan contrast is low.

What does the future hold for retina treatments? Ophthalmologists discussed this, and other exciting developments in retina, during the 78 th Annual Meeting of the All India Ophthalmological Society (AIOC 2020) in Gurugram, India, held earlier this year.

“A very low C-test score is predictive measure of someone who has got both ischemia and edema, like in central retinal vein occlusion (CRVO).” Last, it is helpful in determining optic neuritis. The C-test is currently available for purchase.

Other than barriers, they have also identified promoters of optic nerve regeneration such as beta-tubulin m-RNA in ganglion cells; bcl-2 (B-Cell Lymphoma 2) proto oncogene for ganglion cells regeneration in vitro; and matrix metalloproteinase, identified as a molecule essential for regeneration to foster a receptive transplant environment in eye and CNS tissue. Further investigation is ongoing and Prof. Azad expects this to become a reality within 10 to 15 years.

On Optic Nerve Regeneration Transplants

Will optic nerve regeneration (or transplants) become a reality in the next ten years, or remain as science fiction? Prof. Rajvardhan Azad, president of the India ROP Society, had a chance to find out.

Prof. Azad participated in an eyeball transplantation project headed by Zhongshan Ophthalmic Center’s Director Dr. Yizhi Liu and his team from Zhongshan University (Guangzhou, China). During his presentation, he provided a glimpse of this preliminary study, which reconnected the optic nerve after transection in an animal model.

From the transplant, they identified two barriers to optic nerve regeneration: the BDNF (or brain derived neurotrophic growth factor) that prevents ganglion cells from going into apoptosis; and the CSPG (chondroition sulphate proteoglyutein) in the glial scar, which is an antibody to inhibit

On Surgical Robotics

Surgical robotics have been increasingly used in orthopedics, gastroenterology and neurology. But what about vitreoretinal surgery (VR)?

“The driving force behind the development of robotics in VR surgery has been AI, deep learning and OCT-imaging,” said Dr. Rajiv Raman, during his presentation titled “Robotic Vitreous Surgery Possibilities and Expectations.” In June 2019, the Preceyes Surgical System (PSS) R1.1 to assist surgeons in vitreoretinal procedures received its CE approval. A month before that, the first ever robotic VR surgery was performed in the United Kingdom.

Robotic approaches in ophthalmology have been broadly seen in three areas. 2 First, as an assistive hand held device; the robot works as a smart surgical tool and is manually operated by the surgeon to augment surgical capabilities, such as with tremor filtering or to improve static tasks like drug delivery. It works as a co-manipulator in surgical tasks, such as retinal vein cannulation. Separate robotic manipulators (to which instruments can be attached), are used in motion-controlling by surgeons. Cataract surgeries can even be done remotely through telemanipulation.

“The sensors in the instruments will also increase our safety in surgical performance. The future of VR surgery is actually robotic surgery . . . and it will find applications within the many steps of our routine vitreoretinal procedures,” he concluded.

Researchers are always thinking of new innovations to help patients

On Retinal Plugs

Dr. Ajay Aurora presented his innovative investigation into “Retinal Plug for Retinal Hole in Retinal Detachment.” He shared the fibrin glue used in VR surgery 3 could be a promising technique for the treatment of uncomplicated rhegmatogenous retinal detachment (RD), leading to early visual recovery and requiring no postoperative positioning, while avoiding the usual problems of gas or oil tamponade.

He also foresaw an exciting future for retina plugs made with glue that can be “locked” to rivet a hole, gluing the retina to the RPE. His vision of future retinal plugs involves RD surgeries using the “glue plug.”

On OCTRAR

In another exciting development, Dr. Anand Rajendran presented on “Augmented Reality — GenNext in Retinal Imaging (OCTRAR),” in collaboration with a team from the Indian Institute of Technology (IIT), Madras.

OCTRAR stands for Optical Coherence Tomography Reconstruction and visualization in Augmented Reality (AR). It provides a novel way to reconstruct a 3D model from OCT images and OCT angiograms. The reconstructed model is then visualized in augmented reality with the help of an AR headset. either by placing the AR headset on the head or by using smartphones.

They proposed to display the model on a Heads-Up Display (HUD), powered by a smartphone for easy accessibility. This will provide the physician with an easily accessible mode of the eye, specifically the macula. The doctor will be able to control and interact with the model under examination using a Bluetooth connected joystick.

He said: “To our knowledge, this is the first time such a unique system is being developed for visualization of ocular scans.” His team demonstrated the AR headsets and handphone application during the presentation.

The application of this technology might be relevant to on-field diagnostics, telemedicine and medical AI.

On Vitrectomy for CRAO

Lastly, Dr. Nishikant Borse shared on “Vitrectomy for Central Retinal Artery Occlusion (CRAO) — Future Options.”

There are very limited treatment options non-dissolution of CRAOs. Medical thrombolysis has not worked well because thrombolysis is caused by cholesterol. Surgical vitrectomy gives the advantage of hypotony, directly massaging the CRA and dislodging the embolus with good results.

There are a few limitations to this intervention — for instance, deep embolus. Furthermore, there hasn’t been a consensus of when to intervene within the duration of the CRAO. This is because the survival of retinal cells almost always relies on the amount of residual blood flow and the length of time between onset and treatment.

“Residual blood flow might have been present in eyes where visual improvement was seen after reperfusion,” he said, adding that it was difficult to detect. So, how can the blood flow be quantified more accurately? retina or choroid structure and ocular blood flow based on OCT; and widefield semi-quantitative global flow visualization, using line-scanning Doppler flowmetry (LSDF). This imaging platform enables comprehensive assessment of blood flow in retina and choroid.

“It will enable us to know the amount of ocular and residual flow without injecting a dye. In the future, that will help us to know when to intervene and when not to intervene,” he said.

Another CRAO advance to watch is in endovascular surgery 4 , using a 47-gauge microneedle to directly inject TPA into the central retinal artery. As a result, there were no vitreous hemorrhages after cannulation. “This surgical procedure is very challenging and demands high precision. Thus, the development of robotic technology, such as the robotic armrest, will help in the cannulization — and it will be a very important step achieved in the management of CRAO,” concluded Dr. Borse.

References:

1

2

3

4

Franzco RL, Doba FH. The “C test” for tritan discrimination. Color Res Appl. 2017;43(1):58- 64. de Smet MD, Naus GJL, Faridpooya K, Mura M. Robotic-assisted surgery in ophthalmology. Curr Opin Ophthalmol. 2018; 29:248-253. Tyagi M, Basu S. Glue-assisted retinopexy for rhegmatogenous retinal detachments (GuARD): A novel surgical technique for closing retinal breaks. Indian J Ophthalmol. 2019;67(5):677- 680. Kadonosono K, Yamane S., Inoue M, et al. Intraretinal Arterial Cannulation using a Microneedle for Central Retinal Artery Occlusion. Sci Rep. 2018; 8: 1360.

Editor’s Note:

The 78 th Annual Meeting of the All India Ophthalmological Society (AIOC 2020) took place from 13 to 16 February in Gurugram, India.

Reporting for this story also took place at the AIOC 2020. Media MICE Pte Ltd, CAKE magazine’s parent company, was the media partner at AIOC 2020.